Injection Of Blood Research Articles

Comparing white and gray matter responses to lobar intracerebral hemorrhage in piglets and the effects of deferoxamine

BackgroundIntracerebral hemorrhage (ICH) often impacts patient white matter. However, preclinically, the effects of ICH are mostly studied in rodents with sparse white matter. This study used a lobar porcine ICH model to examine differences in the effects of ICH on white and gray matter as well as the role of the iron chelator deferoxamine (DFX), on attenuation of such injury. MethodsThis two-part study was performed in piglets. Firstly, piglets had a needle (Sham) or 2.5 ml blood injection (ICH) and were euthanized at day 3. Secondly, animals were treated with vehicle or DFX after ICH and were euthanized at day 3. White and gray matter edema, the number of oligodendrocytes (mature and immature) and neurons, and the number of Perls' (iron), ferritin and heme oxygenase (HO)-1 positive cells were examined. ResultsAt day 3, ICH induced greater edema formation in white than gray matter. This marked white matter edema was associated with a loss of mature, but not immature, oligodendrocytes. ICH also induced neuronal death in gray matter. There were also marked increases in Perls', ferritin and HO-1 positive cells after ICH in both white and gray matter, but significantly more in the former. DFX attenuated ICH-induced brain edema in white but not gray matter and this was associated with increased survival of mature oligodendrocytes. DFX also increased survival of neurons in the gray matter and it reduced the number of Perls', ferritin and HO-1 positive cells in both tissue types. ConclusionsWhile there were commonalities in perihematomal changes between white and gray matter after ICH, there was greater edema in white matter which may be linked to the susceptibility of mature oligodendrocytes to ICH injury. Similarly, while DFX reduced perihematomal iron overload in both white and gray matter, it only significantly reduced edema in white matter where it increased the number of mature oligodendrocytes.

Acupoint Autohemotherapy Alleviates Airway Inflammation in Asthmatic Rats via Upregulating Expression of Hemeoxygenase-1.

Acupoint autohemotherapy (AA), a therapeutic technique involving the subcutaneous injection of autologous blood into acupoints, has been empirically validated as safe and effective for treating asthma by alleviating symptoms and decreasing acute attacks, though its mechanism is not well understood. The role of heme oxygenase-1 (HO-1) in AA-induced suppression of asthmatic airway inflammation is examined. Twenty rats were assigned randomly to four groups, namely the Control, OVA, OVA + AA, and (OVA + Snpp) + AA. Rats in the OVA + AA and (OVA + Snpp) + AA received autologous blood injections into acupoints (BL13 and BL23) following OVA challenge. Rats in the (OVA + Snpp) + AA were concurrently subjected to intraperitoneal injections of Snpp, a inhibitor of HO-1. Airway inflammation was evaluated through HE staining, while the concentrations of cytokines in BALF were quantified using ELISA. The mRNA and protein levels of RORγt (Th17-specific transcription factor), Foxp3 (Treg-specific transcription factor), and HO-1 in lung tissue were assessed through qRT-PCR and WB. HE staining indicated that airway inflammation was alleviated in the OVA + AA. The OVA + AA displayed significantly lower counts of total cells and eosinophils in the BALF compared to both the OVA and (OVA + Snpp) + AA. The ELISA demonstrated a significant decrease in levels of pro-inflamatory cytokines (IL-4, IL-17A), and an increase in levels of anti-inflamatory cytokines (IFN-γ, IL-10), in the OVA + AA when compared to both OVA and (OVA + Snpp) + AA. The qRT-PCR and WB analyses revealed an upregulation of HO-1 and Foxp3 expression, and a downregulation of RORγt expression, in the OVA + AA when compared to OVA and (OVA + Snpp) + AA. The involvement of HO-1 in the underlying mechanism responsible for the anti-inflammatory effects of AA is evident.

Efficacy of dextrose prolotherapy for temporomandibular joint hypermobility: A systematic review and meta-analysis

ABSTRACT Objective We reviewed the efficacy of dextrose prolotherapy versus placebo and other active interventions, like autologous blood injection (ABI) and botulinum toxin (BTX), in improving the outcomes of temporomandibular joint (TMJ) hypermobility. Methods We searched PubMed, the Cochrane CENTRAL library, Embase, Scopus, and Web of Science databases to identify randomized controlled trials (RCTs) . Maximal mouth opening (MMO), pain, and frequency of dislocations were analyzed. Results Eight RCTs were included. In comparison with placebo, dextrose prolotherapy was associated with significantly reduced pain and MMO. Comparison of dextrose with ABI revealed no significant difference in MMO. Qualitative analysis showed no significant difference in outcomes in patients who received dextrose prolotherapy and BTX. Conclusions Low-quality evidence suggests that dextrose prolotherapy may reduce MMO and improve pain scores compared to placebo in patients with TMJ hypermobility. Low-quality evidence also suggests that there may be minimal difference in outcomes between dextrose vs ABI and BTX.

Effects of Haptoglobin on Early Brain Injury, Vasospasm, and Lymphatic Drainage After Subarachnoid Hemorrhage in Mice.

Erythrolysis releases free Hb (hemoglobin), which is one of the most upstream and important molecules causing early brain injury and cerebral vasospasm after subarachnoid hemorrhage (SAH). The purpose of this study was to investigate if a Hb scavenger protein Hp (haptoglobin) supplementation prevents early brain injury and cerebral vasospasm and influences the lymphatic drainage mechanism in an established SAH model of mice by a blood injection into the prechiasmatic cistern. This study consisted of 4 parts, with a total of 317 C57BL/6 male mice undergoing sham or SAH modeling, randomly followed by 24-hour intracerebroventricular infusion of no vehicle, 30.1 mg/mL BSA, 30.1 mg/mL Hp (100%; a mixture of Hp1-1, Hp2-1, and Hp2-2), 50% Hp, 25% Hp, and 12.5% Hp solutions from 30 minutes postmodeling. The effects were evaluated at 24 and 48 hours postmodeling. The 100%Hp decreased mortality and brain edema until 48 hours post-SAH and suppressed post-SAH neurological impairments, Hb infiltrations into the perivascular spaces and brain tissues, fibrinogen-positive microthrombi formation, microglial activation, and caspase-dependent neuronal apoptosis, as well as large-vessel vasospasm on India-ink angiography at 24 hours compared with vehicle-treated SAH mice. The Hp solutions up to 50% concentrations also prevented post-SAH neurological impairments, and those up to 25% concentrations suppressed post-SAH neuronal apoptosis and vasospasm development until 48 hours. Immunohistochemical staining of deep cervical and mandibular lymph nodes demonstrated that Hb was increased in the lymphatic sinus after SAH and was further increased by Hp administration in SAH animals. This study first showed that an Hp concentrate prevented early brain injury and cerebral vasospasm by inhibiting Hb penetration into brain tissues and increasing lymphatic drainage of free Hb in an established SAH model of mice.

Perivascular Neutrophil Extracellular Traps Exacerbate Microvasospasm After Experimental Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) can lead to acute or delayed cerebral ischemia. Recent findings have revealed that spasm of microvessels, called microvasospasm, may contribute to SAH-related cerebral ischemia, and perivascular inflammation is considered important in the development of microvasospasms. However, owing to the difficulty in investigating the dynamics of vascular and perivascular events, little is known about the mechanisms underlying microvasospasms. We established an experimental system aiming to investigate the vascular and perivascular pathology of SAH by combining a SAH mouse model with intravital 2-photon imaging. SAH was induced by intracisternal blood injection, and the distribution of erythrocytes, neutrophil behavior, and morphological changes in the pial arterioles were analyzed over time by 2-photon microscopy imaging. To further explore the role of neutrophils and neutrophil extracellular traps (NETs) in microvasospasm, we performed neutrophil depletion by intraperitoneal administration of neutrophil-specific antibody or NETs removal by intracisternal administration of DNase. Erythrocytes were immediately distributed in the perivascular space of the arterioles after SAH induction; neutrophils intensively infiltrated the perivascular space within 2 days and subsequently showed NETosis; and pial arterioles in the same region developed pearl-string-like microvasospasms in the subacute phase. Neutrophil depletion significantly reduced the number of microvasospasms. Furthermore, the removal of perivascular NETs drastically reduced microvasospasms. By establishing a unique experimental system, we demonstrated that perivascular NETs could be a new therapeutic target for microvasospasms.

Development and Validation of a Prechiasmatic Mouse Model of Subarachnoid Hemorrhage to Measure Long-Term Cognitive Deficits.

Controllable and reproducible animal models of aneurysmal subarachnoid hemorrhage (SAH) are crucial for the systematic study of the pathophysiology and treatment of this debilitating condition. However, current animal models have not been successful in replicating the pathology and disabilities seen in SAH patients, especially the long-term neurocognitive deficits that affect the survivor's quality of life. Therefore, there is an unmet need to develop experimental models that reliably replicate the long-term clinical ramifications of SAH - especially in mice where genetic manipulations are straightforward and readily available. To address this need, a standardized mouse SAH model is developed that reproducibly produced significant and trackable long-term cognitive deficits. SAH is induced by performing double blood injections into the prechiasmatic cistern - a simple modification to the well-characterized single prechiasmatic injection mouse model of SAH. Following SAH, mice recapitulated key characteristics of SAH patients, including cerebral edema measured by MRI - an indicator of early brain injury (EBI), neuroinflammation, apoptosis, and long-term cognitive impairment.This newly developed SAH mouse model is considered an ideal paradigm for investigating the complex SAH pathophysiology and identifying novel druggable therapeutic targets for treating SAH severity and SAH-associated long-term neurocognitive deficits in patients.

Neuroprotective Potential of Ethoxzolamide Targeting Oxidative Stress and Inflammation in Experimental Models of Intracerebral Hemorrhage.

As antioxidant and anti-inflammatory agents, carbonic anhydrase inhibitors can exert potentially useful therapeutic effects following central nervous system trauma, including intracerebral hemorrhage (ICH). However, the therapeutic efficacy of ethoxyzolamide (ETZ) as a novel carbonic anhydrase inhibitor for ICH has not yet been determined. An autologous blood injection method was used to establish ICH models, which were then used to establish the effects of intraperitoneal injection of ETZ on ICH. Neuronal damage, apoptotic protein expression, oxidative and inflammatory factor content, microglia marker Iba-1 positivity, hepatic and renal pathological changes, and serum concentrations of hepatic and renal function indices were assessed by Nissl staining, western blotting, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, hematoxylin and eosin (HE) staining, and automatic biochemical analysis in brain tissues. The ICH group showed massive hemorrhagic foci; significant increases in brain water content, modified mouse neurological deficit scoring (mNSS) score, pro-apoptotic protein expression, oxidative factors, pro-inflammatory factors, and Iba-1 positivity; and significant reductions in Nissl body size, anti-apoptotic protein expression, and antioxidant factors, all of which were reversed by ETZ in a dose-dependent manner. ETZ has a good biosafety profile with no significant burden on the human liver or kidneys. The Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway was mildly activated in ICH mice, and was further increased after ETZ injection. Molecular docking experiments revealed that ETZ could dock onto the Nrf2-binding domain of keap1. ETZ, as a novel carbonic anhydrase inhibitor, further activated the Keap1/Nrf2 pathway by docking with the Nrf2-binding domain of keap1, thereby exerting antioxidant, anti-inflammatory, anti-apoptotic, and cerebral neuroprotective effects in ICH mice.

Comparison of the Effectiveness of Autologous Blood Injection and Steroid Injection in Managing Tennis Elbow.

Background Local depot steroid injections can consistently and predictably relieve tennis elbow pain in the short term. Prolotherapy, extracorporeal shockwave therapy, autologous blood, and local injections of platelet-rich plasma (PRP) are examples of novel treatment approaches. Objective The objective of this study is to compare the effectiveness of autologous blood injection and local steroid injection in providing pain relief for patients with lateral epicondylitis (tennis elbow)using the visual analog scale (VAS) over 12 weeks. Methods A descriptive case series was conducted from July 10, 2019, to July 9, 2021, at the Department of Orthopaedic and Spine Surgery, Ghurki Trust Teaching Hospital. A total of 396 patients with tennis elbow, aged 20 to 50 years, were included (198 in each group). Patients managed with non-operative methods and those with other associated injuries in the same elbow were excluded. Group I received an injection of 40 mg of methylprednisolone acetate with 1 ml of 2% lignocaine solution. Group II received an injection of 2 ml of autologous venous blood. The final outcome was assessed at 12 weeks. Results In Group I, the average age of the patients was 36.04 ± 8.26 years, while in Group II, it was 37.23 ± 7.32 years. The male-to-female ratio was2.3:1; 276 (69.81%) of the 396 patients were male, while 120 (30.19%) were female. Group I's mean baseline VASscore was 6.99 ± 0.99, while Group II's mean baseline VAS score was 6.99 ± 1.06 (p = 1.000). Group I had a mean post-therapy VAS score of 3.11 ± 1.62, while Group II had a mean score of 2.48 ± 1.26 (p = 0.0001). About 118 (59.60%) individuals in Group I and 156 (78.79%) patients in Group II experienced pain alleviation from lateral epicondylitis (p = 0.0001). Conclusion This study found that autologous blood injection significantly reduces pain in patients with lateral epicondylitis compared to steroid injection, with a statistically significant p-value of 0.0001. Pain relief was more frequent in the autologous blood group (78.79%) than in the steroid group (59.60%). These findings suggest that autologous blood injections may offer a more effectivetreatment, reducing the need for repeat procedures and improving patient outcomes.

The Role of Complement C1qa in Experimental Intracerebral Hemorrhage.

Evidence indicates that the complement system is activated and plays a role in brain injury after intracerebral hemorrhage (ICH). Most studies have focused on the role of C3, C5 and the membrane attack complex. The purpose of this study was to investigate the potential impact of complement C1q, a key upstream component of the classical pathway, on ICH-induced brain injury. Wild-type (WT) and C1qa knock out (KO) mice were compared using an autologous blood injection ICH model. Magnetic resonance imaging (MRI) was performed on days 1, 3 and 7 and brains harvested on days 3 and 7 for immunohistochemistry to examine brain injury mechanisms. WT and C1qa KO mice also received an intracerebral injection of thrombin, a key factor in ICH-induced brain injury. Following MRI scans, brains were harvested for immunohistochemistry on day 1. In comparison to WT mice, C1qa KO mice had reduced hematoma erythrolysis and neutrophil infiltration after ICH. However, they also had delayed hematoma clearance, which was associated with reduced induction of phagocytic multinuclear giant cells, and increased perihematomal neuronal damage. After thrombin injection, C1qa KO mice had smaller lesion volumes, less neuronal loss, reduced neutrophil infiltration, and less BBB damage. C1qa knockout has beneficial and detrimental effects on ICH-induced brain injury mechanisms, but a consistent beneficial effect after thrombin injection. Strategies to balance the roles of C1q after ICH may represent a promising therapeutic direction.

Dupilumab-related late adverse events in patients with chronic rhinosinusitis with nasal polyps

Background Anti-IL-4 receptor α antibody (dupilumab) has demonstrated favorable sinonasal outcomes for chronic rhinosinusitis with nasal polyps (CRSwNP), which is mainly caused by type 2 inflammation. Although increased blood eosinophil levels and injection site symptoms are frequently observed as acute adverse events (AEs) of dupilumab, limited knowledge is available regarding the late AEs of dupilumab for CRSwNP. Objectives We investigated the late AEs following the initiation of dupilumab treatment for CRSwNP. Material and methods Fifty-one patients with CRSwNP treated with dupilumab for > 3 months were enrolled, and their clinical data were collected from their medical records. Results Six (11.8%) patients experienced late AEs. One case of eczema with pruritus, one case of psoriasis-like dermatitis, two cases of severe rash, one case of malignant lymphoma, and one case of alopecia areata were observed. Skin disorders were the most common late AEs in this study. It is a Th1-inflammatory disease, and its mechanism is thought to be due to the immune imbalance caused by dupilumab. We could not confirm whether malignant lymphoma in our case was caused by dupilumab use. Conclusions and significance Skin disorders are often late AEs associated with dupilumab; therefore, careful monitoring after dupilumab initiation should be considered.

Evaluation of Functional Outcome of Single Dose Intralesional Autologous Blood Vs Corticosteroid Injection in Chronic Plantar Fascitis

Introduction: Plantar fascitis is one of the main underlying causes of acute and chronic heel pain. Diagnosis is mainly based on clinical symptoms and most of the time diagnostic imaging is not required routinely. Corticosteroid injection and autologous blood injection has been a possible means of treatment. Injection of autologous blood can help stimulate a healing response in chronic tendon disorders. Aims: To compare the functional outcome of single dose intra-lesional injection of autologous blood and corticosteroid in chronic plantar fascitis. Methods: This study was done in Nepalgunj medical college and teaching hospital during the period of March 2023 to August 2023 in the department of orthopedics. Sixty patients were enrolled in the study with 30 patients in each group. The patients were selected according to our inclusion and exclusion criteria and diagnosis made on clinical examination alone. The pain status was noted on the visual analog scale and the activity level noted based on the Nirschl stage. The final outcome was based on our scoring system based on the pain status and the activity level at two, four- and twelve-weeks’ duration and graded into four categories as excellent, good, and acceptable and poor. Results: We found that in chronic plantar fascitis, local intralesional steroid injection gives better pain relief and faster return to activities of daily living compared to autologous blood injections. In our study we found that 17.85% had excellent outcome, 35.72% had good outcome and 12% had acceptable outcome in steroid group, whereas in autologous blood group 7.40% had excellent, 22.22% had good and 70.37% had acceptable outcome respectively. Conclusion: Intralesional steroid injection in chronic plantar fascitis have shown to achieve better functional outcome than autologous blood injection.

Gas6/Axl signaling promotes hematoma resolution and motivates protective microglial responses after intracerebral hemorrhage in mice

BackgroundIntracerebral hemorrhage (ICH) stands out as the most fatal subtype of stroke, currently devoid of effective therapy. Recent research underscores the significance of Axl and its ligand growth arrest-specific 6 (Gas6) in normal brain function and a spectrum of neurological disorders, including ICH. This study is designed to delve into the role of Gas6/Axl signaling in facilitating hematoma clearance and neuroinflammation resolution following ICH. MethodsAdult male C57BL/6 mice were randomly assigned to sham and ICH groups. ICH was induced by intrastriatal injection of autologous arterial blood. Recombinant mouse Gas6 (rmGas6) was administered intracerebroventricularly 30 min after ICH. Virus-induced knockdown of Axl or R428 (a selective inhibitor of Axl) treatment was administrated before ICH induction to investigate the protective mechanisms. Molecular changes were assessed using western blot, enzyme-linked immunosorbent assay and immunohistochemistry. Coronal brain slices, brain water content and neurobehavioral tests were employed to evaluate histological and neurofunctional outcomes, respectively. Primary glia cultures and erythrophagocytosis assays were applied for mechanistic studies. ResultsThe expression of Axl increased at 12 h after ICH, peaking on day 3. Gas6 expression did not remarkably changed until day 3 post-ICH. Early administration of rmGas6 following ICH significantly reduced hematoma volume, mitigated brain edema, and restored neurological function. Both Axl-knockdown and Axl inhibitor treatment abolished the neuroprotection of exogenous Gas6 in ICH. In vitro studies demonstrated that microglia exhibited higher capacity for phagocytosing eryptotic erythrocytes compared to normal erythrocytes, a process reversed by blocking the externalized phosphatidylserine on eryptotic erythrocytes. The erythrophagocytosis by microglia was Axl-mediated and Gas6-dependent. Augmentation of Gas6/Axl signaling attenuated neuroinflammation and drove microglia towards pro-resolving phenotype. ConclusionsThis study demonstrated the beneficial effects of recombinant Gas6 on hematoma resolution, alleviation of neuroinflammation, and neurofunctional recovery in an animal model of ICH. These effects were primarily mediated by the phagocytotic role of Axl expressed on microglia.

Seroprevalence of transfusion transmissible infections (TTIS) among blood donors in SOS hospital Heliwa, Somalia

BackgroundA transfusion-transmissible infection (TTI) refers to any infection that can be spread from one person to another through the injection of blood or blood products. The prevalence of these infections varies across countries, influenced by the disease burden within each population. To assess the severity of TTIs, the World Health Organization (WHO) has mandated pre-transfusion blood tests for Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), and syphilis. This study aimed to determine the seroprevalence and trends of TTIs among blood donors at SOS Hospital in Mogadishu, Somalia, from 2016 to 2022. MethodsA retrospective cross-sectional analysis was performed by examining SOS Hospital's blood bank records spanning from 2016 to 2022. The research included all blood donors screened for transfusion-transmissible infections (TTIs) during this period. Data obtained was input and analyzed utilizing Statistical Package for Social Science (SPSS) v.25.0 and Microsoft Excel 2010. Frequencies and percentages were calculated as part of the descriptive statistics. To analyze trends, Chi-square analysis was applied, and statistical significance between variables was determined using the p-value. ResultsThere was a total of 36,296 people donated blood during study period. The majority of blood donors were males (99.8 %), primarily aged between 25 and 44 years (80.4 %) with family donors constituting 80.8 % of the participants. Among 36,296 donors, 1087 (2.99 %) tested positive for transfusion-transmissible infections (TTIs), declining from 4.27 % in 2016 to 1.98 % in 2022. The Chi-Square test confirmed a highly significant reduction in TTIs from 2016 to 2022 (X2 = 57.625, p < 0.0001), indicating a decreasing trend over the seven-year period. Conclusion and recommendationsThis study uncovers a moderate prevalence of transfusion-transmitted infections, indicating a notable decrease over time. Additionally, the findings underscore a gender disparity in blood donation, with replacement donors being predominant. It is imperative to conduct multi-center research endeavors to precisely identify the factors influencing transfusion-transmitted infections among blood donors.

Effect of Levobupivacaine Hydrochloride-Loaded Nanospheres on Delayed Cerebral Vasospasm Following Subarachnoid Hemorrhage in Rabbits

This research was aimed to analyze the mechanism of action of levobupivacaine hydrochloride-loaded nanospheres on delayed cerebral vasospasm following subarachnoid hemorrhage (SAH). Levobupivacaine hydrochloride-loaded nanospheres (LevoBPV Hcl/PLGA) were prepared using the solvent evaporation methodology, with the raw material as a control. The blood drug concentrations were detected by HPLC after subcutaneous and subarachnoid administration in experimental rabbits. Forty New Zealand white rabbits were randomly assigned into Sham group, SAH group, LevoBPV Hcl group (10 mg/kg), and LevoBPV Hcl/PLGA group (10 mg/kg), with 10 rabbits in each group. The SAH model was induced using the double blood injection methodology combined with internal carotid artery ligation. Brain tissue samples were collected on day 7 for pathological characterization, determination of neuronal apoptosis, and measurement of basilar artery diameter and area. The levels of oxidative stress factors (superoxide (SOD), malondiadehyde (MDA), glutathione peroxidase (GSH-Px)) and vasoconstrictor factors (nitric oxide (NO), endothelin-1 (ET-1)) in the cerebrospinal fluid (CSF) were detected using assay kits. The results revealed that the drug loading capacity of LevoBPV Hcl/PLGA was 29.13%, encapsulation efficiency was 87.09%, and the average particle size was 81.43 μm. Under the same dosage, both subcutaneous and subarachnoid administration of LevoBPV Hcl/PLGA exhibited two concentration peaks in the blood drug concentration, with lower concentration values versus LevoBPV Hcl group, and a longer average residence time than LevoBPV Hcl group (P &lt; 0.05). Relative to Sham group, SAH group exhibited decreased diameter and area of the basilar artery, reduced neuronal density, increased neuronal apoptosis rate, decreased levels of SOD, GSH-Px, and NO in the CSF, and increased levels of MDA and ET-1 (P &lt; 0.05). Moreover, LevoBPV Hcl group and LevoBPV Hcl/PLGA group showed increased diameter and area of the basilar artery, higher neuronal density, reduced neuronal apoptosis rate, elevated levels of SOD, GSH-Px, and NO in the CSF, and decreased levels of MDA and ET-1 versus SAH group (P &lt; 0.05). The LevoBPV Hcl/PLGA group exhibited increased diameter and area of the basilar artery, higher neuronal density, reduced neuronal apoptosis rate, elevated levels of SOD, GSH-Px, and NO in the CSF, and decreased levels of MDA and ET-1 versus LevoBPV Hcl group (P &lt; 0.05). In short, LevoBPV HCl-loaded nanospheres can prolong the in vivo residence time of subcutaneous and subarachnoid administration, reduce the maximum blood drug concentration, and enhance drug safety. Furthermore, these nanospheres can inhibit neuronal apoptosis following SAH, regulate oxidative stress and vasoconstrictor factor expression, thereby suppressing the occurrence of delayed cerebral vasospasm and alleviating brain tissue damage.

In situ implantable DNA hydrogel for diagnosis and therapy of postoperative rehemorrhage following intracerebral hemorrhage surgery.

Postoperative rehemorrhage following intracerebral hemorrhage surgery is intricately associated with a high mortality rate, yet there is now no effective clinical treatment. In this study, we developed a hemoglobin (Hb)-responsive in situ implantable DNA hydrogel comprising Hb aptamers cross-linked with two complementary chains and encapsulating deferoxamine mesylate (DFO). Functionally, the hydrogel generates signals upon postoperative rehemorrhage by capturing Hb, demonstrating a distinctive "self-diagnosis" capability. In addition, the ongoing capture of Hb mediates the gradual disintegration of the hydrogel, enabling the on-demand release of DFO without compromising physiological iron-dependent functions. This process achieves self-treatment by inhibiting the ferroptosis of neurocytes. In a collagenase and autologous blood injection model-induced mimic postoperative rehemorrhage model, the hydrogel exhibited a 5.58-fold increase in iron absorption efficiency, reducing hematoma size significantly (from 8.674 to 4.768 cubic millimeters). This innovative Hb-responsive DNA hydrogel not only offers a therapeutic intervention for postoperative rehemorrhage but also provides self-diagnosis feedback, holding notable promise for enhancing clinical outcomes.

Preliminary study of extracorporeal shock wave alleviating joint capsule fibrosis caused by internal bleeding of knee joint in rats

ABSTRACT Purpose Joint contracture is a common disease in clinical practice, joint bleeding is an important factor affecting the progression of joint contracture. This study aimed to explore the effect of extracorporeal shock wave on alleviating joint capsule fibrosis caused by intra-articular hemorrhage in rats. Methods Forty two SD rats were randomly divided into seven groups. Perform simple fixation and fixation after blood injection separately. Measure the range of motion of each group’s knee joints and calculate the corresponding degree of contraction. Use HE staining and Masson staining to detect the number of anterior joint capsule cells and collagen deposition. Detection of changes in Wnt1, β-catenin protein expression in joint capsule using Western blotting. Results Compared to group C, the degree of knee joint contracture in M1 and M2 groups of rats increased, and collagen deposition, cell number and Wnt1, β-catenin protein expression also increased accordingly. Compared to M1 and M2 groups, the degree of knee contraction in E1 and E2 groups were reduced, while collagen deposition, cell number and Wnt1, β-catenin protein expression were decreased, and the degree of joint contracture in NR1 and NR2 groups showed no significant improvement. Compared to NR1 and NR2 groups, the degree of knee contraction in E1 and E2 groups were reduced, while collagen deposition, cell number and Wnt1, β-catenin protein expression were decreased. Conclusions Both rat models of knee joint contracture were successful, and joint bleeding can exacerbate joint contracture. Extracorporeal shock waves alleviate joint capsule fibrosis caused by intra-articular bleeding in rats.

The potential of disulfiram as a drug to improve the prognosis after the onset of subarachnoid hemorrhage

Subarachnoid hemorrhage due to rupture of intracranial aneurysms has a poor outcome, making this disease being the social problem. Inflammation evoked by the increase in intracranial pressure and the clot in the subarachnoid space after the onset of SAH exacerbates neuronal death and vasospasm, resulting in the poor outcome and severe aftereffects. Here, FROUNT mediates CCR2 and CCR5 signaling as an intracellular molecule binding to these chemoattractant receptors which facilitate the migration of inflammatory cells, such as macrophages, in situ to trigger inflammation there. Animal model of subarachnoid hemorrhage was established in rats through intrathecal injection of autologous blood. The effect of the FROUNT inhibitor, disulfiram, on survival rate, neuronal death in hippocampus or vasospasm was then examined. The intrathecal administration of disulfiram significantly suppressed the infiltration of CD68-positive macrophages and myeloperoxidase-positive neutrophils toward the clot in the cistern in situ. In this condition, disulfiram ameliorated the death of animals after the onset of subarachnoid hemorrhage in rats. In addition, disulfiram suppressed both the two major events after subarachnoid hemorrhage, the neuronal death in hippocampus and vasospasm. The pharmacological inhibition of CCR2 and CCR5 signaling by disulfiram could thus be the therapeutic strategy to improve the outcome of subarachnoid hemorrhage.

Selective injury of thalamocortical tract in neonatal rats impairs forelimb use: model validation and behavioral effects.

Unilateral brain injury in neonates results in largely contralateral hand function in children. Most research investigating neurorehabilitation targets for movement recovery has focused on the effects of brain injury on descending motor systems, especially the corticospinal tract. However, a recent human study demonstrated that sensory tract injury may have larger effects on dexterity than motor tract injury. To validate that the sensory tract injury impairs dexterity, we modeled the most common site of sensory tract injury in neonates by targeting the thalamocortical tract. In the postnatal day 7 rats, we used three types of lesions to the thalamocortical tract: periventricular blood injection, photothrombotic lesion, and electrolytic lesion. To test the sensitivity and specificity of these techniques, viral tracers were injected into the primary sensory or motor cortex immediately after injury. Electrolytic lesions were the most specific and reproducible for inducing a lesion compared to the other two methods. Electrolytic lesions disrupted 63% of the thalamocortical tract, while sparing the adjacent corticospinal tract in the internal capsule. To measure the impact on dexterity, the cylinder exploration and pasta handling tests were used to test the changes of forelimb use at 8 weeks after injury when the rats reached maturity. Lesions to the thalamocortical tract were associated with a significant decrease in the use of the contralateral forelimb in the cylinder task, and the degree of impairment positively correlated with the degree of injury. Overall, specific sensory system lesions of the thalamocortical tract impair forelimb use, suggesting a key role for skilled movement.

Validation of a simplified model for subarachnoid hemorrhage in mice.

Subarachnoid hemorrhage (SAH) represents a severe injury to the brain and is associated with a high mortality (40%). Several experimental SAH models are described in the literature requiring specialized equipment and a high degree of surgical expertise. Our goal was to validate a simplified, cost-effective model to permit future studies of SAH. SAH was induced by injection of homologous blood into the cisterna magna. Perfusion-fixation then perfusion of gelatinous India ink was performed. Brains and brainstems were collected and imaged for analysis of cerebral vasospasm. Triphenyl tetrazolium chloride (TTC) staining was used to analyze brain tissue cell death 24 hours following stroke. A composite neuroscore was utilized to assess SAH-related neurologic deficits. Anterior cerebral artery and basilary artery diameters were significantly reduced at 24 hours post SAH induction. Middle cerebral artery diameter was also reduced; however, the results were not significant. TTC staining showed no infarcted tissue. Neuroscores were significantly lower in the SAH mice, indicating the presence of functional deficits. This simplified model of SAH elicits pathological changes consistent with those described for more complex models in the literature. Therefore, it can be used in future preclinical studies examining the pathophysiology of SAH and novel treatment options.

Comparing autologous blood, corticosteroid, and a combined injection of both for treating lateral epicondylitis: a randomized clinical trial

BackgroundBecause lateral epicondylitis is a common musculoskeletal disorder that affects the forearm's extensor tendons, an effective therapeutic approach should reverse the degeneration and promote regeneration. This study aimed to compare the efficacies of autologous blood (AB) injection, corticosteroid (CS) injection, and a combined injection of both in treating lateral epicondylitis (LE), hypothesizing that the combined approach might offer immediate symptom resolution and a lower recurrence.Materials and methodsA total of 120 patients diagnosed with lateral epicondylitis were systematically distributed among three distinct therapeutic injection groups. Those in the AB group were administered 1 ml of autologous venous blood mixed with 2 ml of 2% prilocaine HCl. Participants in the CS category were given 1 ml of 40 mg methylprednisolone acetate mixed with 2 ml of 2% prilocaine HCl. Meanwhile, patients in the combined group received a mixture containing 1 ml each of autologous venous blood and 40 mg methylprednisolone acetate along with 1 ml of 2% prilocaine HCl. Prior to receiving their respective injections, a comprehensive assessment of all participants was carried out. Follow-up assessments were subsequently conducted on days 15, 30, and 90 utilizing metrics of the patient-rated tennis elbow evaluation (PRTEE) and measurements of hand grip strength (HGS).ResultsOne patient dropped out from the combined group, and 119 patients completed the trial. No complications were recorded during the course of follow-up. By day 15, all groups had demonstrated significant PRTEE improvement, with CS showing the most pronounced reduction (p = 0.001). However, the benefits of CS had deteriorated by day 30 and had deteriorated further by day 90. The AB and AB + CS groups demonstrated sustained improvement, with AB + CS revealing the most effective treatment, achieving a clinically significant improvement in 97.4% of the patients. The improved HGS parallelled the functional enhancements, as it was more substantial in the AB and AB + CS groups (p = 0.001), corroborating the sustained benefits of these treatments.ConclusionsThe study concluded that while AB and CS individually offer distinct benefits, a combined AB + CS approach optimizes therapeutic outcomes, providing swift and sustained functional improvement with a lower recurrence rate. These findings have substantial clinical implications, suggesting a balanced, multimodal treatment strategy for enhanced patient recovery in LE.Level of evidence: Randomized clinical trial, level 1 evidence.Trial registration: NCT06236178.