Brain Tissue Damage Research Articles

Efficacy of enhanced extracorporeal counterpulsation combined with atorvastatin in the treatment of cognitive impairment after stroke.

Cerebral apoplexy patients are prone to cognitive impairment, and it is very important to choose appropriate treatment methods to improve their cognitive impairment after stroke. To evaluate the effects of enhanced external counterpulsation (EECP) in conjunction with atorvastatin on cognitive function, neurotransmitter levels, and the repair of brain tissue damage in patients with cognitive impairment due to stroke. In this retrospective study, data from 60 patients with poststroke cognitive impairment due to stroke who were treated in our hospital from February 2021 to July 2022 were analyzed and divided into a treatment group (n = 30) and a control group (n = 30) according to the different nursing methods applied. Patients in the treatment group received EECP in addition to atorvastatin, while those in the control group received atorvastatin alone. Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and activities of daily living (ADL) scale scores were compared between the two groups. Additionally, the two groups were compared in terms of serum acetylcholine (ACh), acetylcholinesterase (AChE), nitric oxide (NO), endothelin-1 (ET-1), β2-microglobulin (β2-MG), glial fibrillary acidic protein (GFAP), and visinin-like protein 1 (VILIP-1) in the serum. Blood flow measurements from the anterior cerebral artery (ACA), middle cerebral artery (MCA) and posterior cerebral artery (PCA) were compared between the two groups before and after treatment, and the pulsatility index (PI) and resistance index (RI) of each artery were determined. MMSE, MoCA, and ADL scores all improved in both groups following treatment, with the study group showing more improvement than the control group (P < 0.05). After treatment, there were statistically significant increases in both ACh and NO levels, whereas decreases occurred in AChE, ET-1, β2-MG, VILIP-1, and GFAP, levels and the PI and RI of the left-ACA, right-ACA, left-MCA, right-MCA, left-PCA, and right-PCA. The study group showed greater gains in all metrics than the control group (P < 0.05). EECP combined with atorvastatin is effective in the treatment of cognitive impairment after stroke and can effectively improve the cognitive function, neurotransmitter levels, and brain tissue damage status of patients.

Hesperidin counteracts chlorpyrifos-induced neurotoxicity by regulating oxidative stress, inflammation, and apoptosis in rats.

Chlorpyrifos (CPF), considered one of the most potent organophosphates, causes a variety of human disorders including neurotoxicity. The current study was designed to evaluate the efficacy of hesperidin (HSP) in ameliorating CPF-induced neurotoxicity in rats. In the study, rats were treated with HSP (orally, 50 and 100mg/kg) 30min after giving CPF (orally, 6.75mg/kg) for 28 consecutive days. Molecular, biochemical, and histological methods were used to investigate cholinergic enzymes, oxidative stress, inflammation, and apoptosis in the brain tissue. CPF intoxication resulted in inhibition of acetylcholinesterase (AChE) and butrylcholinesterase (BChE) enzymes, reduced antioxidant status [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH)], and elevation of malondialdehyde (MDA) levels and carbonic anhydrase (CA) activities. CPF increased histopathological changes and immunohistochemical expressions of 8-OHdG in brain tissue. CPF also increased levels of glial fibrillary acidic protein (GFAP) and nuclear factor kappa B (NF-κB) while decreased levels of nuclear factor erythroid 2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α). Furthermore, CPF increased mRNA transcript levels of caspase-3, Bax, PARP-1, and VEGF, which are associated with apoptosis and endothelial damage in rat brain tissues. HSP treatment was found to protect brain tissue by reducing CPF-induced neurotoxicity. Overall, this study supports that HSP can be used to reduce CPF-induced neurotoxicity.

Urolithin B Attenuates Cerebral Ischemia–reperfusion Injury by Modulating Nrf2-regulated Anti-oxidation in Rats

Ischemia-reperfusion (IR) induces a wide range of irreversible injuries. Cerebral IR injury (IRI) refers to additional brain tissue damage that occurs after blood flow is restored following cerebral ischemia. Currently, no established methods exist for treating IRI. Oxidative stress is recognized as a primary mechanism initiating IRI and a crucial focal target for its treatment. Urolithin B, a metabolite derived from ellagitannins, antioxidant polyphenols, has demonstrated protective effects against oxidative stress in various disease conditions. However, the precise mechanism underlying UB’s effect on IRI remains unclear. In our current investigation, we assessed UB's ability to mitigate neurological functional impairment induced by IR using a neurological deficit score. Additionally, we examined cerebral infarction following UB administration through TTC staining and neuron Nissl staining. UB's inhibition of neuronal apoptosis was demonstrated through the TUNEL assay and Caspase-3 measurement. Additionally, we examined UB's effect on oxidative stress levels by analyzing malondialdehyde (MDA) concentration, superoxide dismutase (SOD) activity, and immunohistochemistry analysis of inducible nitric oxide synthase (iNOS) and 8-hydroxyl-2′-deoxyguanosine (8-OHdG). Notably, UB demonstrated a reduction in oxidative stress levels. Mechanistically, UB was found to stimulate the Nrf2/HO-1 signaling pathway, as evidenced by the significant reduction in UB's neuroprotective effects upon administration of ATRA, an Nrf2 inhibitor. In summary, UB effectively inhibits oxidative stress induced by IR through the activation of the Nrf2/HO-1 signaling pathway. These findings suggest that UB holds promise as a therapeutic agent for the treatment of IRI.

EFFECTIVENESS OF PHYSICAL THERAPY AND REHABILITATION IN IMPROVING MOTOR SKILLS AND MENTAL FUNCTION IN CHILDREN WITH CEREBRAL PALSY

Cerebral palsy was first described by William John Little in 1846. There are many definitions of cerebral palsy that vary from author to author. However, we can say that cerebral palsy (CP) is a chronic non-progressive brain damage, postural and body motility disorder. Apart from sensorimotor abnormalities, some cases are accompanied by mental disorders as well as disorders of cognitive functions. It can occur during pregnancy, at birth or during the postnatal period, ie. prenatal, perinatal and postnatal - equally in both sexes. There are different classifications of cerebral palsy: according to changes in muscle tone, according to topographic features and according to the severity of the clinical picture.According to changes in muscle tone, they are divided into: Spastic form, Athetoid form, Ataxic form, Hypotonic form and Mixed form. According to the topography they are classified as: Diplegia, Quadriplegia, Hemiplegia, Triplegia and Monoplegia Physical therapy program is determined based on the clinical form of the disease. When determining a rehabilitation program, the principle of an individual approach is followed. Rehabilitation includes: physical medicine, kinesitherapy, reflex exercises according to Vojta, manual massage, thermotherapy, education of parents for rehabilitation at home; orthopedic aids; special education techniques. The aim of this study is to determine the role and impact of Physical Medicine and Rehabilitation in the treatment of children with Cerebral Palsy in early childhood. The research was conducted at the University of Southeast Europe - (Stul University) at the Faculty of Health Sciences in the Department of Physical Therapy and Rehabilitation, over a period of 6 months, from the beginning of April to the end of September 2023. 61 patients with cerebral palsy are included in the research, of which 28 are male, and the remaining 33 patients are female. The patients included in the research are classified into groups according to: gender, age and clinical form of cerebral palsy. The treatment of Cerebral Palsy (CP) has a complex character and includes medical, pedagogical and social rehabilitation. The individual tasks of the rehabilitation are determined after a functional examination of the motor abilities, where the main role is played by muscle tone, normal and pathological reflex motor activity, in the period up to 1 year of age. The goal of treatment with Physical Therapy and Rehabilitation is to achieve correct and timely development of movements and correction of pathological movement stereotypes (models), which occurred as a result of brain tissue damage. As for the motor deficit, kinesitherapy plays a major role. Established modern methods for kinesitherapy are the specialized methods for neuromuscular re-education of Vojta and Bobath. The Rood and Rabat methods werw also be used to facilitate the required movements and train coordination. Physical therapy and rehabilitation combined with kinesitherapy have an exceptional positive effect in: prevention of pathological primitive reflexes;creation and automation of normal active movements;saving irregular positions of the limbs and the whole body;establishment of balance and correct pattern of movement; fight against spasticity, secondary contractures and deformities; improvement of coordination and awareness of the body in relation to the environment.

Meta-analysis of stereotactic hematoma removal and craniotomy hematoma removal in the treatment of hypertensive intracerebral hemorrhage in the elderly.

A large number of clinical studies suggested that surgery might be a better choice than conservative treatment for treating hypertensive intracerebral hemorrhage in the middle-aged and elderly. Stereotactic puncture can reduce the mass effect caused by hematoma, reduce the intervention of body homeostasis, reduce brain tissue damage, and improve the prognosis of patients with cerebral hemorrhage. This meta-analysis aims to evaluate the efficacy of stereotactic puncture and craniotomy in elderly patients with hypertensive intracerebral hemorrhage. A search strategy was designed to search in databases, including PubMed, Embase, Cochrane Central Register of Controlled Trials, CNKI, Wanfang database and relevant references. Literature on the efficacy and safety of different surgical methods for hypertensive cerebral hemorrhage in the middle-aged and elderly were retrieved. The search time was until August 17, 2022. Keywords included "hypertensive intracerebral hemorrhage," "stereotactic hematoma removal," "craniotomy." After the literature search, 2 researchers independently conducted literature screening, quality evaluation of included trials and data extraction. RevMan5.4 software was used to perform a Meta-analysis on the operation time, hospital stay, postoperative Glasgow Coma Scale (GCS) score, postoperative daily activity ability, postoperative complications and neurological prognosis scores included in the included studies. A total of 1988 samples were included in 9 studies. 1022 patients underwent stereotactic hematoma removal, and 968 patients underwent craniotomy hematoma removal. The orientation group had more advantages in the length of hospital stay, postoperative disability, pulmonary infection, intracranial infection and digestive tract ulcer, and the difference was statistically significant (P < .05). In addition, the length of stay (I²= 83%) of the included articles had good homogeneity (I²< 50%), and there was no significant difference between the 2 groups in operation time, postoperative GCS score, postoperative daily activity ability, and neurological prognosis score (P > .05). The meta-analysis indicate that compared to craniotomy for hematoma removal, stereotactic hematoma removal can reduce the postoperative disability rate, intracranial infection rate, lung infection rate, and digestive tract ulcer rate in middle-aged and elderly patients with hypertensive intracerebral hemorrhage.

Mechanisms of ferroptosis in hypoxic-ischemic brain damage in neonatal rats

This study was to explore the mechanism of ferroptosis and hypoxic-ischemic brain damage in neonatal rats. The neonatal rat hypoxic-ischemic brain damage (HIBD) model was established using the Rice-Vannucci method and treated with the ferroptosis inhibitor liproxstatin-1. Cognitive assessment was performed through absentee field experiments to confirm the successful establishment of the model. Brain tissue damage was evaluated by comparing regional cerebral blood flow and quantifying tissue staining. Neuronal cell morphological changes in the rats' cortical and hippocampal regions were observed using HE and Nissl staining. ELISA was performed to determine GPX4, GSH and ROS expression levels in the rats' brain tissues, and Western blotting to assess the expression levels of 4-HNE, GPX4, GSS, ACSL4, SLC7A11, SLC3A2, TFRC, FHC, FLC, HIF-1α, and Nrf2 proteins in rat brain tissues. Compared to the Sham group, the HIBD group exhibited a significant decrease in cerebral blood perfusion, reduced brain nerve cells, and disordered cell arrangement. The use of the ferroptosis inhibitor effectively improved brain tissue damage and preserved the shape and structure of nerve cells. The oxidative stress products ROS and 4-HNE in the brain tissue of the HIBD group increased significantly, while the expression of antioxidant indicators GPX4, GSH, SLC7A11, and GSS decreased significantly. Furthermore, the expression of iron metabolism-related proteins TFRC, FHC, and FLC increased significantly, whereas the expression of the ferroptosis-related transcription factors HIF-1α and Nrf2 decreased significantly. Treatment with liproxstatin-1 exhibited therapeutic effects on HIBD and downregulated tissue ferroptosis levels. This study shows the involvement of ferroptosis in hypoxic-ischemic brain damage in neonatal rats through the System Xc−-GSH-GPX4 functional axis and iron metabolism pathway, with the HIF-1α and Nrf2 transcription factors identified as the regulators of ferroptosis involved in the HIBD process in neonatal rats.

Brief isoflurane administration as an adjunct treatment to control organophosphate-induced convulsions and neuropathology.

Organophosphate-based chemical agents (OP), including nerve agents and certain pesticides such as paraoxon, are potent acetylcholinesterase inhibitors that cause severe convulsions and seizures, leading to permanent central nervous system (CNS) damage if not treated promptly. The current treatment regimen for OP poisoning is intramuscular injection of atropine sulfate with an oxime such as pralidoxime (2-PAM) to mitigate cholinergic over-activation of the somatic musculature and autonomic nervous system. This treatment does not provide protection against CNS cholinergic overactivation and therefore convulsions require additional medication. Benzodiazepines are the currently accepted treatment for OP-induced convulsions, but the convulsions become refractory to these GABAA agonists and repeated dosing has diminishing effectiveness. As such, adjunct anticonvulsant treatments are needed to provide improved protection against recurrent and prolonged convulsions and the associated excitotoxic CNS damage that results from them. Previously we have shown that brief, 4-min administration of 3%-5% isoflurane in 100% oxygen has profound anticonvulsant and CNS protective effects when administered 30min after a lethal dose of paraoxon. In this report we provide an extended time course of the effectiveness of 5% isoflurane delivered for 5min, ranging from 60 to 180min after a lethal dose of paraoxon in rats. We observed substantial effectiveness in preventing neuronal loss as shown by Fluoro-Jade B staining when isoflurane was administered 1h after paraoxon, with diminishing effectiveness at 90, 120 and 180min. In vivo magnetic resonance imaging (MRI) derived T2 and mean diffusivity (MD) values showed that 5-min isoflurane administration at a concentration of 5% prevents brain edema and tissue damage when administered 1h after a lethal dose of paraoxon. We also observed reduced astrogliosis as shown by GFAP immunohistochemistry. Studies with continuous EEG monitoring are ongoing to demonstrate effectiveness in animal models of soman poisoning.

The potential of a combined cell‐based therapy and rehabilitation approach for stroke recovery

AbstractActivation of neuroprotective and particularly later neurorestorative mechanisms after stroke attempts to restore or compensate for lost functions. This potentially opens a wide window for restorative therapies to promote brain repair and improve long‐term functional recovery. Although extensively demonstrated in the preclinical setting, the efficacy of cell‐based therapies in stroke patients has been modest at best, if any at all. Translational failure may be due to the ineffective survival and integration of transplanted cells in pro‐death stroke microenvironments that are not conducive for the structural reconstruction of damaged brain tissue and repair‐related network reorganization. Optimal systemic delivery, timing, cell product, and dose remain open as well. Fortunately, a better understanding of the brain plasticity mechanisms underlying stroke recovery has ushered in a combination approach of cell‐based therapy and rehabilitation that is aimed at achieving additive, synergistic, or even maximal beneficial effects. This novel combination therapy is not only targeted at promoting exogenous and endogenous cell survival and augmenting stand‐alone restorative mechanisms but also at utilizing rehabilitation to facilitate a graft–host structural and functional integration and plasticity that would effectively remodel stroke tissue and restitute lost functions. This review presents an overview of the combination of cell‐based therapy and experimental rehabilitation in stroke models. It also discusses associated shortcomings as well as proposes strategies to address them and help facilitate the advancement of this combination approach.

Thermodynamics of amyloid formation

AbstractBackgroundIs amyloid formation an exothermic process with the potential to damage brain tissue by local hyperthermia? In our study we aim to find answers to the above question. Several proteins, i.e. lysozyme and amyloid‐β peptide, known to form amyloid structures are investigated primarily by differential scanning calorimetry (DSC) in order to determine their thermodynamic properties.MethodExperiments in DSC are complemented by a set of other biophysical methods in order to clarify molecular parameters for the evaluation of the heat capacity measurements.ResultFor this purpose a seeded amyloid formation assay has been designed. In this assay the structural conversion of a given amount of monomeric protein is accelerated and synchronized by the addition of preformed amyloid fibril fragments to result in reproducible heat bursts caused by amyloid formation.ConclusionFirst results are reported and the measured enthalpies are related to known enthalpies from protein structural conversion processes.

Low-intensity focused ultrasound modulation of the paraventricular nucleus to prevent myocardial infarction–induced ventricular arrhythmia

BackgroundOur previous study showed that light-emitting diode modulation of the hypothalamic paraventricular nucleus (PVN), which is the control center of the sympathetic nervous system, might attenuate neuroinflammation in the PVN and prevent ventricular arrhythmias (VAs) after myocardial infarction (MI). Low-intensity focused ultrasound (LIFU) has deeper penetration than does light-emitting diode, while its effect on the PVN has not been reported. ObjectiveThis study aimed to explore the effect of LIFU modulation of the PVN on the inducibility of post-MI VAs. MethodsFifty-four Sprague-Dawley rats were randomly divided into acute control (n = 12, 22.22%), acute MI (AMI, n = 12, 22.22%), AMI + LIFU (n = 12, 22.22%), chronic control (n = 6, 11.11%), chronic MI (CMI, n = 6, 11.11%), and CMI + LIFU (n = 6, 11.11%) groups. MI was induced by left anterior artery ligation, and electrocardiographic recording for 0.5 hours after MI and programmed electrophysiological stimulation were used to test the vulnerability of VAs. Peripheral sympathetic neural activity was assessed by measuring left stellate ganglion neural activity. Finally, hearts and brains were extracted for Western blotting and histopathological analysis, respectively. ResultsCompared with the AMI group, AMI-induced VAs (P < .05) and left stellate ganglion neural activity (P < .05) were significantly attenuated in the AMI + LIFU group. In addition, LIFU resulted in a significant reduction of microglial activation in the PVN and expression of inflammatory cytokines in the peri-ischemic myocardium. In the CMI + LIFU group, there was no obvious tissue damage in the brain. ConclusionLIFU modulation of the PVN may prevent the incidence of post-MI VAs by attenuating MI-induced sympathetic neural activation and inflammatory response.

Anti-diabetics and the Prevention of Dementia: A Systematic Review.

Type 2 diabetes mellitus (T2DM) is a worldwide epidemic that is only increasing as the years progress, and as of 2019, affecting over 37 million. T2DM is a chronic condition caused by reduced insulin secretion and increased insulin resistance. Due to insulin not operating at optimal conditions, blood glucose rises and remains high, thus disturbing metabolic hemostasis. Many complications can arise from T2DM, such as coronary vascular disease, kidney damage, eye damage, and, quite significantly, dementia. It is theorized that dementia from T2DM stems from the fact that the brain is susceptible to hyperglycemic conditions, which are promoted by the increase in insulin resistance of target cells in the central nervous system. This directly affects cognitive processes and memory, which correlates to decreased temporal and front lobes volume. The risk of diabetic complications can be minimized with therapeutic interventions such as oral-antidiabetic (OAD) agents and insulin. Several OADs are on the market, but the first-line agent is metformin, a biguanide that decreases glucose production and increases insulin sensitivity. This paper aims to determine if currently prescribed OADs can help slow cognitive decline and reduce the risk and incidence of dementia as a complication of T2DM. Studies found that, for the most part, all OADs except sulfonylureas (SU) significantly slowed the decline of cognitive function and reduced the risk and incidence of dementia. SU's were shown to increase the risk of dementia in most studies. Of all the OADs, thiazolidinediones may be the most beneficial drug class for reducing the risk of dementia in T2DM patients. Future research should focus on whether early intervention with specific classes of OADs can not only improve glycemic control, leading to decreased hyperglycemia but also prevent the build-up of damaged brain tissue and help to reduce the risk and incidence of dementia in patients with T2DM.

Assessment of time to death, brain tissue damage and clinical signs of consciousness in mature Jersey x Holstein cattle receiving a secondary penetrating captive bolt gunshot at the poll or frontal sinus locations

Providing cattle with a good death is an ethical imperative for the dairy industry. When using a penetrating captive bolt gun (PCBG), a secondary (adjunctive) method is currently recommended. Some farms prefer to apply the secondary shot in the poll location whereas others prefer the frontal-sinus location. Unfortunately, little is known about the efficacy of these alternative secondary shot locations. The purpose of this study was to compare clinical signs of consciousness and time to death for 2 different secondary PCBG shot locations in mature Jersey x Holstein cross dairy cattle. Data was collected contemporaneously at 6 dairy operations located in the Midwest U.S. After receiving the first PCBG shot in the frontal-sinus location, cattle requiring euthanasia (n = 46) were randomly assigned to receive a secondary PCBG shot in either the poll (Frontal- Poll) or the frontal-sinus location (Frontal-Frontal) and continuously monitored for clinical signs of consciousness (corneal and palpebral reflex, rhythmic breathing, threat response, etc.) and heartbeat. Signs of consciousness were rarely observed immediately following the first frontal-sinus shot. The median time period when the last heartbeat was heard (7-8 min) did not differ between groups (P = 0.253) nor did gross brain trauma scores (P = 0.247). We conclude the location of the secondary PCBG shot (frontal vs poll) does not seem to impact time to death or gross brain trauma scores. These findings confirm results of previous research involving younger cattle and suggest additional research is needed to better understand the effect of different PCBG locations.

Effects of miR-204-5p and Target Gene EphB2 on Cognitive Impairment Induced by Aluminum Exposure in Rats.

Aluminum is a common environmental neurotoxin. Aluminum ions can cross the blood-brain barrier and accumulate in different brain regions, damage brain tissue, and cause cognitive impairment, but the molecular mechanism of aluminum neurotoxicity is not precise. This study investigated the effects of miR-204-5p, target gene EphB2, and downstream signaling pathway NMDAR-ERK-CREB-Arc on cognitive dysfunction induced by aluminum exposure. The results showed that the learning and memory of the rats were impaired in behavior. The accumulation of aluminum in the hippocampus resulted in the damage of nerve cell morphology in the CA1 region of the hippocampus. The expression level of miR-204-5p was increased, and the mRNA and protein expressions of EphB2, NMDAR2B, ERK1/2, CREB, and Arc were decreased. The results indicated that the mechanism of impaired learning and memory induced by aluminum exposure might promote the expression of miR-204-5P and further inhibit the expression of the target gene EphB2 and its downstream signaling pathway NMDAR-ERK-CREB-Arc.

Curcumin alleviates Alzheimer’s disease by inhibiting inflammatory response, oxidative stress and activating the AMPK pathway

BackgroundAlzheimer’s disease (AD) is a common degenerative brain disorder with limited therapeutic options. Curcumin (Cur) exhibits neuroprotective function in many diseases. We aimed to explore the role and mechanism of Cur in AD. Materials and MethodsFirstly, we established AD mice by injecting amyloid-β1–42 (Aβ1–42) solution into the hippocampus. Then, the AD mice received 150 mg/kg/d Cur for 10 consecutive days. The Morris water maze test was conducted to evaluate the cognitive function of the mice by hidden platform training and probe trials. To assess the spatial memory of the mice, spontaneous alternation behavior, the number of crossing the novel arm and the time spent in the novel arm during the Y-maze test was recorded. Hematoxylin and eosin (H&E) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNAL) assay were performed to assess the pathological damage and apoptosis of brain tissues. The number of damaged neurons was inspected by Nissl staining. Immunohistochemical staining was then performed to detect Aβ1–42 deposition. The levels of tumor necrosis factor-α (TNF-a), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in serum and hippocampus, the contents of super oxide dismutase (SOD) and malondialdehyde (MDA) in brain tissues were assessed by enzyme-linked immunosorbent assay (ELISA). Additionally, B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), RelA (p65) protein expressions and Adenosine 5′-monophosphate-activated protein kinase (AMPK) phosphorylation were tested using Western blot. ResultsCur not only improved cognitive function and spatial memory, but also alleviated the pathological damage and apoptosis of brain tissues for AD mice. Meanwhile, upon Cur treatment, the number of damaged neurons in AD mice was decreased, the level of Aβ1–42 in AD mice was significantly decreased. Furthermore, the AD mice treated with Cur exhibited lower TNF-a, IL-6, IL-1β and MDA levels and a higher SOD content. Besides, Cur also downregulated p65 expression and upregulated AMPK phosphorylation. ConclusionCur may improve AD via suppressing the inflammatory response, oxidative stress and activating the AMPK pathway, suggesting that Cur may be a potential drug for AD.

Application of the Minkowski Distance Similarity Method in Case-Based Reasoning for Stroke Diagnosis

A Stroke is a cerebrovascular disease characterized by impaired brain function due to damage or death of brain tissue caused by reduced or blocked blood and oxygen flow to the brain. Expert systems can be used as learning aids for medical students to diagnose stroke. Medical records of stroke cases can be reused as a reference for diagnosing stroke when there are new cases, known as the case-based reasoning (CBR) method. This study implements the Minkowski distance similarity method in CBR to calculate the similarity value between cases, where each similar case has the same solution. This study uses the Minkowski distance similarity method in CBR to obtain the most optimal value of r and the most appropriate threshold value in the expert system for stroke diagnosis. The diagnosis process is carried out by inputting the patient's condition, symptoms, and risk factors. Then the system will calculate the similarity value and take the case with the highest similarity value as the solution, providing that the similarity value must be greater than or equal to the threshold value. Based on system testing, the best accuracy value was achieved by applying a threshold value of 75 with an r value of 3 or 4, with an accuracy rate of 88,89%, a recall value of 88%, and a precision of 100%.

PENYULUHAN TENTANG UPAYA MENGHINDARI STROKE PADA IBU RUMAH TANGGA BERUSIA 30 TAHUN KE ATAS

Stroke is a disease that is a problem in the world, 85% of the world's population is at risk of stroke. Stroke is a chronic disease that has a dangerous impact. by impaired blood circulation to the brain due to arterial blood vessels due to deposits blood in the veins, rupture of the veins blood or abnormalities in the condition of the blood itself resulting in a lack of oxygen supply and nutrients to the brain which causes brain tissue damage. lack of knowledge of patients, families and the general public about stroke, its signs, symptoms, and good lifestyle for stroke sufferers such as eating instant food. community service about stroke if properly explained can be encouraging stroke sufferers to immediately seek treatment so that the impact of death and disability can be overcome or minimized.

RBIO-06. COMBINING FLASH RADIOTHERAPY WITH GD2-CAR T CELL IMMUNOTHERAPY IN DIFFUSE INTRINSIC PONTINE GLIOMA

Abstract Diffuse Intrinsic Pontine Glioma (DIPG) is the leading cause of brain tumor related deaths in pediatric cancers. DIPG is completely lethal, and palliative radiation therapy (RT) to control symptoms is currently the standard-of-care treatment for DIPG, therefore effective treatment is urgently needed. In recent phase 1 clinical trials, the promising potential for using chimeric antigen receptor T cell immunotherapy against the disialoganglioside GD2 (GD2-CART) has been established, where 75% of patients exhibited clinical and radiographic improvement. There has also been emerging evidence advocating for the combined use of GD2-CART therapy with conventional radiation (CONV-RT) to enhance the immune response in other solid brain tumors. Ultra-high dose rate radiotherapy, abbreviated as FLASH-RT, is an emerging radiation technique shown to reduce normal brain tissue damage while preserving tumor control, as compared to CONV-RT. It is currently unknown how FLASH-RT will affect CART therapy. We hypothesize that effective treatment for DIPG can be achieved by combining FLASH-RT with GD2-CART immunotherapy. We have shown FLASH-RT to equivocally kill DIPG cells as well as the standard-of-care, CONV-RT; Given the neurological tissue sparing effects of FLASH-RT, this radiotherapy alone could be an improvement for DIPG treatment. Additionally, we have validated that GD2 is highly expressed in our DIPG cell line, suggesting high GD2-CART target specificity. Additionally, we have found that GD2 expression on DIPG tumor cells remains unchanged upon treatment with FLASH-RT. Therefore, we can utilize FLASH-RT to target GD2 CART while sparing normal tissue and minimizing neurotoxicity, allowing for a promising avenue of combination treatment for this devastating pediatric cancer.

SURG-31. DEFINING THE NEW POSSIBILITIES FOR CESIUM BRACHYTHERAPY IN PATIENTS WITH PERIVENTRICULAR GBM

Abstract INTRODUCTION Re-irradiation of patients with external beam radiotherapy (EBRT) for recurrent glioblastoma (GBM) continues to present a therapeutic dilemma due to a high risk of radiation induced necrosis (RN). In contrast, brachytherapy represents a safer, more conformal radiation option aimed at optimizing local control while minimizing the risk of brain tissue damage. Immediate intra-operative implantation with brachytherapy prevents tumor repopulation and offers patients two procedures in one setting. However, due to the risk of seed migration, surgical resection and brachytherapy in periventricular regions was deemed unachievable. In heavily pretreated periventricular GBM, where further EBRT is complicated by RN, a barrier between the ventricular lining and tumor cavity is needed to prevent seed migration. We present two patients where such a barrier allowed successful implantation of brachytherapy to improve disease control. METHODS Two patients, previously treated with surgery and EBRT, presented with recurrent GBM abutting the ventricles. Following GTR of the tumors, a barrier was created by patching the ventricle with Gelfoam to prevent seed migration. Intraoperative brachytherapy implantation of suture stranded Cs-131 seeds (Isoray) for patient 1 and collagen embedded Cs-131 (GammaTile) for patient 2 was performed. A total of 20 Cs-131 seeds on strings threaded through Surgicel, and 6 GammaTiles (24 Cs-131 seeds), were used implanted in patients 1 and 2, respectively. Surgicel covered the implanted seeds and the resection cavity filled with Adherus. RESULTS Post-operative CT scan demonstrated all 20 Cs-131 seeds and 24 Cs-131 seeds in the surgical cavities of patients 1 and 2, respectively, and had serial post operative imaging with MRI scans showing Cs-131 seeds layering surgical cavity, as late as 6 months in total follow up. To date, both patients have had durable local control and no seed migration.

Effect of royal jelly on acrylamide-induced neurotoxicity in rats

Royal Jelly (RJ) is a natural product made by nurse bees known for its multiple therapeutic properties. The research aims to discover the ability of RJ to improve the hematological alterations and neurotoxicity caused by acrylamide (AA). The study rats were separated equally into four groups (6 in each group), the control group, the AA (38.27 mg/kg bw) group, the RJ (150 mg/kg bw) + AA group, and the RJ (300 mg/kg bw) + AA group. Blood and brain samples were collected after 10 days to evaluate haematological and biochemical parameters and to examine histopathological and immunohistochemistry. The administration of AA increased the level of malondialdehyde (MDA), decreases levels of haematological parameters, superoxide dismutase (SOD), reduced glutathione (GSH), brain-derived neurotrophic factor (BDNF), neurotransmitters (serotonin, dopamine, and acetylcholine), and cleaved caspase-3, as well as increase the damage to the brain tissues. Meanwhile, RJ improved levels of haematological parameters, oxidative stress parameters (MDA, SOD, and GSH), BDNF, neurotransmitters, cleaved caspase-3, and brain tissue damage induced by AA. The study demonstrated the protective impact of RJ against the haematological alterations and neurotoxicity caused by AA.

Protective effect of heme chloride on hypoxia-induced tissue injury in mice.

Heme chloride (Hemin) is an in vitro purified form of natural heme and an important raw material for anti-anemia and antitumor drugs. This study aims to analyze the protective effect of Hemin on tissue damage in low-pressure oxygen chamber simulated plateau hypoxic mice, and explore its role in anti-plateau hypoxia. Thirty male BALB/c mice were randomly divided into a blank group, a positive drug group (acetazolomide, 200 mg/kg), a Hemin low-dose group (15 mg/kg), a Hemin medium-dose group (30 mg/kg), and a Hemin high-dose group (60 mg/kg) with intraperitoneal injection. The anti-hypoxic activity of Hemin was explored by atmospheric closed hypoxia experiment and the optimal dose was screened. Thirty-six male BALB/c mice were randomly divided into a blank group, a hypoxia group, a positive drug group, and a Hemin high-dose group. The plasma inflammatory factor levels and oxidative stress indicators malondialdehyde (MDA), glutataione (GSH), and superoxide dismutase (SOD) levels of myocardium, brain, lung, and liver tissues were measured in different groups with hypoxia for 24 h. The degree of histopathological damage of mice was observed with HE staining. The degree of protection of Hemin against tissue hypoxia injury was detected with the hypoxia probe piperidazole. Compared with the blank group, the survival time of mice in the positive drug group, the Hemin medium-dose group, and high-dose group was significantly extended (all P<0.05), with the highest prolongation rate in the Hemin high-dose group. Compared with the hypoxia group, mice in the Hemin high-dose group showed a significant increase in SOD level and GSH content of brain tissue, and a significant decrease in MDA content of lung tissue (all P<0.05). The results of HE staining and hypoxia probe showed that Hemin had a significant protective effect on the damage of liver, heart, brain and lung tissues of mice with hypoxia, and the most obvious effect on that of the brain tissue. Hemin has an effect of improvement on oxidative stress and inflammatory response caused by hypoxia, and has obvious protective effect on tissue damage caused by hypoxia.