Middle Cerebral Artery Thrombosis Research Articles

Results of assessing cerebral vasospasm following subarachnoid hemorrhage using transcranial doppler ultrasound

SUMMARY Objective: Review the results of assessing cerebral vasospasm after subarachnoid hemorrhage using transcranial doppler ultrasound. Subjects and methods: A retrospective, cross-sectional descriptive study was performed on 39 patients with subarachnoid hemorrhage treated at the Neurology Center, Bach Mai Hospital from January 2020 to September 2023. Results: The mean age of the study group was 55.12 ± 14.33. The age group distribution with the highest incidence is 41-50 years old with a rate of 35.9%. The male/female ratio is 20/19. The most common symptoms were headache (97.4%), nausea and vomiting (92.3%), The least common symptoms were convulsions and hemiplegia in 5.1% of subjects. The most common clinical severity assessed by the Hunt and Hess scale is level 2 (59%), followed by level 3 (23.1%), level 4 (10.2%), and level 1 (5.1%). Evaluation of Fisher scale found that the most common fisher level is level 4 with a rate of 33.6%, followed by level 3 (28.2%), level 1 (25.6%), the least common is grade 2 with 2.6%. The results of the second transcranial Doppler ultrasound performed on the sixth to eighth day of the disease is the time with the highest rate of vasospasm, showing the most vasospasm cerebral artery is the middle cerebral artery: right middle cerebral artery. 35.9%, left middle cerebral artery 12.8%. Next is anterior cerebral artery spasm: right anterior cerebral artery 23.1%, left anterior cerebral artery 2.6%. Right posterior cerebral artery 10.3%, left posterior cerebral artery 5.1%. Compared to the gold standard for diagnosing vasospasm, which is 128-slices MSCT, transcranial Doppler ultrasound has a sensitivity of 0.91, a specificity of 0.88, a positive predictive value of 0.91, and a negative predictive value of 0.88. The appropriateness of transcranial Doppler ultrasound and 128-slices computed tomography scan in diagnosing cerebral vasospasm after subarachnoid hemorrhage is very high, Kappa coefficient = 0.791, statistically significant with p < 0.05. Conclusion: Clinical symptoms of the disease are very diverse and non-specific, the most common symptom being headache is 97.4%. The most common Hunt and Hess scale to assess clinical severity is 2, however the most common Fisher scale is 4. Middle cerebral artery thrombosis has the highest rate of spasm, followed by the anterior cerebral artery. Compared to the gold standard for diagnosing vasospasm, which is 128-slices MSCT, transcranial Doppler ultrasound has a sensitivity of 0.91, a specificity of 0.88, a positive predictive value of 0.91, and a negative predictive value of 0.88

1011 A Rare Case of Left Sided Hemiparesis Following a Pneumatic Gun-Shot Injury to Left Anterior Chest Wall in a 13-Year-Old Boy

Abstract Introduction Even though pneumatic weapons rarely cause severe direct trauma, pellet embolisation can lead to unexpected, catastrophic events. Case Report A 13-year-old, previously healthy boy was injured by an accidentally fired pneumatic gun, while playing with his twin brother. He sustained a penetrating wound to left anterior chest wall and resultant bleeding was self-limiting. He was hospitalised within 15minutes. On admission, he was hemodynamically stable with normal Respiratory, Cardiovascular and Neurological system findings. Entry wound measuring 5*5 mm was present at 5th intercostal space just left to the sternum. No exit wound was detected. Initial chest radiograph and ultra-sound abdomen and chest were normal. 2D echocardiogram revealed only a very thin layer(3mm) of pericardial effusion. Four hours later, He developed a focal seizure followed by left sided hemiparesis. Urgent NCCT brain and carotid artery duplex showed a high dense pellet in right internal carotid artery at the level of petrous temporal bone and hypo-dense Middle Cerebral Artery (MCA) suggestive of right MCA thrombosis. He was transferred to a tertiary care centre. Interventional radiological and endo-vascular attempts of pellet retrieval have been failed. Ischemic stroke pursued with worsening cerebral oedema; thus decompression craniotomy was performed on day 3. He is currently being rehabilitated in a specialised centre. Conclusions High degree of suspicion should be maintained on the possibility of projectile embolisation, in pneumatic gun-shot injuries, especially in the absence of an exit wound. Extensive early investigations should be performed to localise the projectile and retrieval should be planned.

Central Retinal Artery Occlusion in Young Adults at High Altitude: Thin Air, High Stakes.

Rana, Vipin, Pradeep Kumar, Sandeepan Bandopadhyay, Vijay K. Sharma, Meenu Dangi, Dattakiran Joshi, Sanjay Kumar Mishra, Satyabrat Srikumar, and V.A. Arun. Central retinal artery occlusion in young adults at high altitude: thin air, high stakes. High Alt Med Biol. 00:000-000, 2024.-We present five cases of young security personnel who were posted at high altitude (HA) for a duration of at least 6 months and presented with a sudden decrease of vision in one eye. The diagnosis of central retinal artery occlusion (CRAO) was made in all patients. Fundus fluorescein angiography and optical coherence tomography of the macula supported the diagnosis. None of these cases had any preexisting comorbidities. Erythrocytosis was noticed in all patients, and two of them had hyperhomocysteinemia. Four out of five patients showed either middle cerebral artery or internal carotid artery (ICA) thrombosis on computed tomography angiography. The patients were managed by a team of ophthalmologist, hematologist, vascular surgeon, and neurologist. In cases of incomplete ICA occlusion, patients were managed surgically. However, in the case of complete ICA occlusion, management was conservative with antiplatelet drugs. This case series highlights HA-associated erythrocytosis and hyperhomocysteinemia as important risk factors for CRAO in young individuals stationed at HA.

Left middle cerebral artery and sigmoid sinuses thrombosis in a female patient with Crohn's disease

Introduction: Neurologic manifestations in patients with inflammatory bowel disease (IBD) appear to be more common than in the past. However, vascular events in IBD are still a rare presentation and were reported in few cases. Case presentation: A 48-year-old female patient known case of Crohn’s disease presented with sudden onset aphasia, headache, blurring of vision, and decreased level of consciousness for 2 hours. The patient looked ill, confused, agitated, and aphasic. Neurologic examination shows dysarthria and 0/5 power of the right upper and lower extremity. A brain CT without contrast was ordered and showed acute ischemic stroke. The patient received tPA (alteplase) immediately in the intensive care unit and was under observation. On admission, brain CT angiography, MRI, and MRV were performed, which showed middle cerebral artery and sigmoid sinuses thrombosis. The patient has undergone cerebral catheterization, and an MCA stent was inserted. Post catheterization, the patient’s right-sided extremity power was improved to 3/5. She was discharged from the hospital after 13 days in good general condition except for her expressive aphasia. Conclusion: To the best of our knowledge, here we report the first case presented with both; cerebral venous sinus thrombosis and cerebral arteries thrombosis in a patient with IBD. Clinicians must be considered ischemic stroke in any patients with IBD presented with acute neurological manifestation, and an urgent interventional approach must be performed.

Interventions in cerebrovascular emergencies among patients with Paroxysmal nocturnal haemoglobinuria - A word of caution

IntroductionParoxysmal nocturnal haemoglobinuria (PNH) is a clonal hematopoietic disorder, where there is deficiency of glycosylphosphatidylinositol (GPI) anchored proteins in the cell membrane, leading to increased complement sensitivity of red blood cells, intravascular hemolysis and vascular inflammation. Arterial and venous strokes in patients with PNH are a rarity posing significant diagnostic and therapeutic challenges. We report our experience with management of PNH patients with cerebrovascular emergencies. MethodsWe report 2 patients with PNH, one who was previously diagnosed with PNH and had arterial stroke, the other had an index presentation of cerebral venous sinus thrombosis (CVT) and was subsequently diagnosed with PNH. We also present the systematic review of literature reporting similar cases, highlighting the challenges in management. ResultsBoth patients presented to our centre with cerebrovascular emergency. The first patient was a diagnosed with PNH, and presented with left hemispheric infarction caused by thrombosis of middle cerebral artery. He was thrombolysed and underwent mechanical thrombectomy, which was unsuccessful in view of repeated re – thrombosis of the vessel. The patient survived with significant disability. The second patient had severe cerebral venous sinus thrombosis with large right hemispheric hemorrhagic venous infarction. She underwent emergency decompressive hemicraniectomy complicated by massive blood loss and disseminated intravascular coagulation. She subsequently had recurrent life threatening intracranial bleed secondary to platelet transfusions, thrombocytopenia, and use of contrast agents. She progressed to develop Budd Chiari syndrome and was initiated on Eculuzimab. She became transfusion independent, however remained in minimally conscious state and succumbed to sepsis. ConclusionsManagement of arterial and venous strokes is complex in patients with PNH. Invasive procedures and platelet transfusions are to be avoided in acute thrombosis, till robust evidence is available establishing the safety of the same in patients with PNH. Eculuzimab is a promising option, but far from reach for patients in developing countries.

SUSCEPTIBILITY WEIGHTED IMAGING TECHNIQUE UTILITY IN DIVERSE NEUROLOGICAL ENTITIES

Background: Susceptibility Weighted Imaging (SWI) is a novel modality based upon GE (Gradient Echo) sequences that employ differences in susceptibility of various paramagnetic as well as diamagnetic substances that aid in the better diagnosis of various neurological entities such as intracranial tumors, vascular malformations, arterial stroke, venous hemorrhagic infarcts. Objective:To assess utility of SWI in various neurological diseases. Methods: The retrospective observational study was held in a tertiary care medical center in India in 2021. Multiple neurological diseases on SWI were analyzed in 100 patients with neurological complaints. The inclusion criteria included patient of all age group who presented with neurological signs and symptoms. The exclusion criteria included presence of post-operative non-compatible orthopedic hardware and patients with cardiac pacemakers, cochlear implants in situ. Results: The majority were males and > 60 years (23%) in age. Among 100 patients, most had tumors (18%), followed by trauma (16%), arterial stroke (15%), and hemorrhage (14%). Most of 14 patients with hemorrhage have intraparenchymal hemorrhage 9 (64.29%). There were10 patients with venous sinuses thrombosis and 15 cases with arterial stroke amongst whom most had middle cerebral artery thrombosis (46.66%). Most 13 patients with vascular pathologies had amyloid angiopathy 4 (30.77%). The majority of tumors were primary 15 (83.33%) with 10 (66.67%) newly diagnosed tumors, 11 (61.11%) tumors had a hemorrhage, 3 (16.67%) presented with calcification, and 4 (22.22%) had both hemorrhage and calcification. According to SWI grading of the tumor by intratumoral susceptibility score (ITSS), the majority were in grade III. On the correlation of SWI grading with MR Spectroscopy (MRS) and MR perfusion (MRP) study, 6 (100%) grade III patients showed hyperperfusion on MRP with raised choline/Creatinine ratio. SWI was better than CT (P<0.05) in detecting trauma, hemorrhage, cerebral venous sinus thrombosis, vascular pathologies, and tumors. Conclusion: SWI is a helpful imaging tool in neuroradiological practice and should be incorporated into standard procedures. It is beneficial in identifying hemorrhages, low-flow vascular abnormalities, diffuse axonal injury, and neurodegenerative illnesses. In addition, it is a supplementary sequence in the stroke by distinguishing calcium from hemorrhage in the brain and categorizing brain tumors.

MULTIPLE TROMBOSIS IN CHILD WITH POST COVID-19 INFECTION

Introduction: SARS CoV-2 infection can cause acute, as well as chronic damage to the cardiovascular system. Blood vessel dysfunction and clot formation, as suggested by elevated D-dimer levels, are thought to play a significant role in morbidity, as well as in mortality in Covid-19 patients, leading to clots causing pulmonary embolisms and ischemic events within the brain1. Aim: To confirm the correlation between SARS CoV-2 infection and possibility for vascular complication, including thrombotic brain lesion. Materials: Detailed patient’s history, physical examination particularly noting the neurological status and locomotor skills, as well as blood analysis with hemostasis and d-dimers, serology for SARS CoV-2 IgG antibodies and PCR swab were all part of the diagnostic process for this patient. Methods: Computed tomography and brain MRI with angiography were main imaging tools used in the diagnostic process. Results: Thrombosis of the left middle cerebral artery was confirmed on brain MRI with angiography in a patient recovered from SARS CoV-2 infection, noted with high levels of IgG antibodies to the particular virus and elevated D-dimer levels, presenting with symptomatic right sided hemiparesis. Conclusion: Some of the patients recovered from SARS CoV 2 infection can develop ischemic stroke. This link is confirmed by elevated levels of IgG antibodies in patient’s serum against SARS CoV-2. This kind of vascular post viral complication can cause different kind of disability, presented with neurological impairment and coagulation disorders. The prognose is improving with anticoagulant and physical therapy started early.2 Keywords: Thrombosis, SARS Cov-2, Brain, Hemiparesis

Susceptibility Weighted Imaging: An Effective Auxiliary Sequence That Enhances Insight Into the Imaging of Stroke

Aim: To evaluate the utility of susceptibility-weighted imaging (SWI) sequence in stroke imaging and assess supplemental information provided by SWI in an acute stroke scenario.Materials and methods: In this study, the appearance of cerebrovascular stroke on the SWI images were analyzed in 50 patients who presented with acute-onset neurological symptoms.Results: Brain MRI with SWI was performed on 50 patients presenting with acute neurological symptoms. The majority were males, 32/50 (64%) and 18/50 (36%) were females. Most of the patients were in the age group > 60 years (36%), followed by 50-60 years (22%). Most of the patients had bilateral pathology, 20 (40%). The majority of patients had supratentorial lesions 34 (68%). Among 50 patients, the majority of patients had arterial stroke 20 (40%) and cerebral venous sinus thrombosis (CVST) 20 (40%) followed by amyloid angiopathy five (10%), and five (10%) had hypertensive microhemorrhage. Among the 20 patients with arterial stroke, the majority had middle cerebral artery (MCA) thrombosis 10 (50%) and among the 20 patients with venous thrombosis, eight (40%) patients had hemorrhagic infarcts. SWI was better as compared to computed tomography (CT) (P<0.05) in the detection of hemorrhagic transformation of arterial infarct, cerebral hemorrhagic venous sinus thrombosis, hemorrhagic venous infarct, hypertensive microhemorrhage, and cerebral amyloid angiopathy.Conclusion: SWI is a useful imaging sequence that provides additional information on stroke patients. SWI requires only an additional three-four minutes to perform and can be easily incorporated into standard stroke protocol. SWI can identify various features such as hemorrhage, intraarterial thrombus, or concomitant microbleeds that are of prognostic value and affect therapeutic decisions.

Abstract TP21: The Role Of Interleukin-1α Cytokine In Poststroke Inflammation

Stroke remains the second leading cause of death globally, with a total of 5.5 million deaths in 2016 and an estimated global lifetime risk of stroke for those aged 25 years or older at 24.9%. A key feature of stroke and poststroke injury is the inflammatory response, which is driven by a variety of pro-inflammatory cytokines to include interleukin-1 (IL-1). Evidence from pre-clinical studies have demonstrated a deleterious effect of IL-1 poststroke with a beneficial effect observed after blocking IL-1 in both pre-clinical and clinical settings. The IL-1 family has both IL-1β and IL-1α forms, and although IL-1β has been most closely studied, the distinct roles of both IL-1 isoforms during poststroke inflammation is largely unknown. In this study, we examined the contribution of IL-1α in ischemic stroke. We characterized the spatio-temporal effect of IL-1 in the brain after stroke using an in vivo model of middle cerebral artery thrombosis in an inducible IL-1α knockout mouse through topical application of FeCl3. We found that IL-1α precedes IL-1β expression after ischemic stroke and is restricted to microglia whereas IL-1β is expressed by both neutrophils and microglia. Intriguingly, microglial IL-1α deletion does not influence brain damage after ischemic stroke, and furthermore does not influence cerebral blood flow or neutrophil infiltration and IL-1β expression up to 24h after ischemic stroke. Pathway analysis following RNAseq suggests that microglial IL-1α regulates neuronal activity through CREB signaling. In vitro studies in Neuro2a (N2a) murine cell line additionally show neuronal activity regulation through CREB signaling via microglial IL-1α after oxygen glucose deprivation and reperfusion (OGD/R) model of stroke. As the role of IL-1α in stroke has yet to be fully elucidated, future experiments using both murine and in vitro models will clarify the role that IL-1α has in the pathogenesis of stroke and its relevance to inflammatory features posttroke, which may lead to future therapeutic insight.

A pilot behavioural and neuroimaging investigation on photothrombotic stroke models in rhesus monkeys

BackgroundIschemic stroke leads to a long-term disability in humans and no efficient clinical therapy exists to date. The middle cerebral artery occlusion (MCAO) model in non-human primates has shown to be of value for translational stroke research.New methodIn the current study, a photothrombotic (PT) stroke model was established in rhesus monkeys with either a proximal or distal segment of middle cerebral artery (MCA) thrombosis. This study is the first that compares the two approaches of PT stroke in monkeys using behavioral and physiological measurements and MRI scans. ResultsThe experiment found that infarct occurred in the MCA target regions, with all monkeys having impaired behavior reflected by deficits in neurologic function, and motor and cognition in object retrieval detour (ORD) task. The monkeys with distal MCA thrombosis developed with sequential photo-irritations of the Sylvian fissure zone, adjacent central anterior gyrus and central posterior gyrus, had similar impairments with respect to behavior and showed a tendency of a small edema volume with proximal MCA thrombosis at days 4 and 7 post PT stroke. Comparison with existing methodsThe distal MCA thrombosis developed with sequential photo-irritations might provide a consistent and well-tolerated focal ischemia in rhesus monkeys, compared with other PT stroke models which usually were singly conducted on the animal’s motor cortex and had a temporal effect. ConclusionsThe sequentially photo-irritated PT stroke model is a promising ischemic stroke model in rhesus monkey for studying human stroke pathology and physiology and for new therapies development.

Abstract P767: Understanding the Role of Microglial Il-1α After Stroke

The role of inflammation driven by the pro-inflammatory cytokine interleukin-1 (IL-1) during poststroke injury has been the focus of intense research. Indeed, pre-clinical studies have demonstrated the deleterious actions of IL-1 after stroke, whilst blocking its actions is beneficial in pre-clinical and clinical settings. Whilst most studies have focused on the role of IL-1β, the role of IL-1α during poststroke inflammation has been largely overlooked and very little has been done to examine the selective contribution of each IL-1 isoform in ischaemic stroke. In this study, we have investigated the contribution of IL-1α to ischaemic and haemorrhagic stroke. Methods : in vivo model of middle cerebral artery thrombosis through topical application of FeCl3 (40%) (n=4/group (4, 24, 72h) histology, n=6 /group (4, 24, 72 ) qPCR) in vivo model of haemorrhagic stroke induced by using the collagenase model (intra-striatal injection of collagenase VII-S, 0.045U) (n=4/group (4, 24h) histology). We first investigated the spatio-temporal expression of IL-1 in the brain after ischaemic stroke using an in vivo model of middle cerebral artery thrombosis through topical application of FeCl3 (n=4-6/group). We observed IL-1α positive microglia as early as 4 hours after ischaemic stroke. At 24 hours we observed IL-1α and also IL-1β positive microglia, moreover, IL-1β was also expressed by neutrophils and monocytes. These results have been confirmed by qPCR. Interestingly, we observed similar results after haemorrhagic stroke, induced by using the collagenase model, whereby IL-1α expression in microglia precedes IL-1β expression (n=4/group). The early expression of IL-1α in microglia in both models suggest a critical role for the microglial response during sterile inflammation. To further investigate the role of microglial IL-1α, we have generated a conditional IL-1α mouse mutant crossed with CX3CR1 Cre-ERT2 mice to induce a specific deletion of IL-1α in microglia. Future experiments using this genetic model will clarify the role of IL-1α during the acute phase of strokes.

Effect of electroacupuncture on glial fibrillary acidic protein and nerve growth factor in the hippocampus of rats with hyperlipidemia and middle cerebral artery thrombus.

Electroacupuncture (EA) has been shown to reduce blood lipid level and improve cerebral ischemia in rats with hyperlipemia complicated by cerebral ischemia. However, there are few studies on the results and mechanism of the effect of EA in reducing blood lipid level or promoting neural repair after stroke in hyperlipidemic subjects. In this study, EA was applied to a rat model of hyperlipidemia and middle cerebral artery thrombosis and the condition of neurons and astrocytes after hippocampal injury was assessed. Except for the normal group, rats in other groups were fed a high-fat diet throughout the whole experiment. Hyperlipidemia models were established in rats fed a high-fat diet for 6 weeks. Middle cerebral artery thrombus models were induced by pasting 50% FeCl3 filter paper on the left middle cerebral artery for 20 minutes on day 50 as the model group. EA1 group rats received EA at bilateral ST40 (Fenglong) for 7 days before the thrombosis. Rats in the EA1 and EA2 groups received EA at GV20 (Baihui) and bilateral ST40 for 14 days after model establishment. Neuronal health was assessed by hematoxylin-eosin staining in the brain. Hyperlipidemia was assessed by biochemical methods that measured total cholesterol, triglyceride, low-density lipoprotein and high-density lipoprotein in blood sera. Behavioral analysis was used to confirm the establishment of the model. Immunohistochemical methods were used to detect the expression of glial fibrillary acidic protein and nerve growth factor in the hippocampal CA1 region. The results demonstrated that, compared with the model group, blood lipid levels significantly decreased, glial fibrillary acidic protein immunoreactivity was significantly weakened and nerve growth factor immunoreactivity was significantly enhanced in the EA1 and EA2 groups. The repair effect was superior in the EA1 group than in the EA2 group. These findings confirm that EA can reduce blood lipid, inhibit glial fibrillary acidic protein expression and promote nerve growth factor expression in the hippocampal CA1 region after hyperlipidemia and middle cerebral artery thrombosis. All experimental procedures and protocols were approved by the Animal Use and Management Committee of Beijing University of Chinese Medicine, China (approval No. BUCM-3-2018022802-1002) on April 12, 2018.

Virtual reality simulation of neuroendovascular intervention improves procedure speed in a cohort of trainees.

Background:Realistic virtual reality (VR) simulators have greatly expanded the tools available for training surgeons and interventionalists. While this technology is effective in improving performance in many fields, it has never been evaluated for neuroendovascular procedures. This study aims to determine whether VR is an effective tool for improving neuroendovascular skill among trainees.Methods:Trainees performed two VR revascularizations of a right-sided middle cerebral artery (MCA) thrombosis and their times to procedural benchmarks (time to enter internal carotid artery [ICA], traverse clot, and complete procedure) were compared. To determine whether the improvement was case specific, trainees with less procedural exposure were timed during VR left-sided ICA (LICA) aneurysm coiling before or after performing MCA thrombectomy simulations. To determine the value of observing simulations, medical students were timed during the right MCA revascularization simulations after watching other VR procedures.Results:Trainees significantly improved their time to every procedural benchmark during their second MCA revascularization (mean decrease = 1.08, 1.57, and 2.24 min; P = 0.0072, 0.0466, and 0.0230). In addition, time required to access the LICA during aneurysm coiling was shortened by 0.77 min for each previous VR right MCA revascularization performed (P = 0.0176; r2 = 0.71). Finally, medical students’ MCA revascularization simulation times improved by 0.87 min for each prior simulation viewed (P < 0.0221; r2 = 0.96).Conclusion:Both performance and viewing of simulated procedures produced significant decreases in time to reach neuroendovascular procedural benchmarks. These data show that VR simulation is a valuable tool for improving trainee skill in neuroendovascular procedures.

Extent of Ischemic Brain Injury After Thrombotic Stroke Is Independent of the NLRP3 (NACHT, LRR and PYD Domains-Containing Protein 3) Inflammasome.

Background and Purpose- A major process contributing to cell death in the ischemic brain is inflammation. Inflammasomes are multimolecular protein complexes that drive inflammation through activation of proinflammatory cytokines, such as IL (interleukin)-1β. Preclinical evidence suggests that IL-1β contributes to a worsening of ischemic brain injury. Methods- Using a mouse middle cerebral artery thrombosis model, we examined the inflammatory response after stroke and the contribution of the NLRP3 (NACHT, LRR and PYD domains-containing protein 3) inflammasome to ischemic injury. Results- There was a marked inflammatory response after stroke characterized by increased expression of proinflammatory cytokines and NLRP3 and by recruitment of leukocytes to the injured tissue. Targeting NLRP3 with the inhibitor MCC950, or using mice in which NLRP3 was knocked out, had no effect on the extent of injury caused by stroke. Conclusions- These data suggest that the NLRP3 pathway does not contribute to the inflammation exacerbating ischemic brain damage, contradicting several recent reports to the contrary.

Biohybrids of scaffolding hyaluronic acid biomaterials plus adipose stem cells home local neural stem and endothelial cells: Implications for reconstruction of brain lesions after stroke.

Endogenous neurogenesis in stroke is insufficient to replace the lost brain tissue, largely due to the lack of a proper biological structure to let new cells dwell in the damaged area. We hypothesized that scaffolds made of hyaluronic acid (HA) biomaterials (BM) could provide a suitable environment to home not only new neurons, but also vessels, glia and neurofilaments. Further, the addition of exogenous cells, such as adipose stem cells (ASC) could increase this effect. Athymic mice were randomly assigned to a one of four group: stroke alone, stroke and implantation of BM, stroke and implantation of BM with ASC, and sham operated animals. Stroke model consisted of middle cerebral artery thrombosis with FeCl3 . After 30 days, animals underwent magnetic resonance imaging (MRI) and were sacrificed. Proliferation and neurogenesis increased at the subventricular zone ipsilateral to the ventricle and neuroblasts, glial, and endothelial cells forming capillaries were seen inside the BM. Those effects increased when ASC were added, while there was less inflammatory reaction. Three-dimensional scaffolds made of HA are able to home newly formed neurons, glia, and endothelial cells permitting the growth neurofilaments inside them. The addition of ASC increase these effects and decrease the inflammatory reaction to the implant. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1598-1606, 2019.

Lysophosphatidic acid LPA1 and LPA3 receptors play roles in the maintenance of late tissue plasminogen activator-induced central poststroke pain in mice

We developed a mouse model for central post-stroke pain (CPSP), a centrally-originated neuropathic pain (NeuP). In this mode, mice were first injected with Rose Bengal, followed by photo-irradiation of left middle cerebral artery (MCA) to generate thrombosis. Although the MCA thrombosis was soon dissolved, the reduced blood flow remained for more than 24 h due to subsequent occlusion of microvessels. This photochemically induced thrombosis (PIT) model showed a hypersensitivity to the electrical stimulation of both sides of paw, but did not show any abnormal pain in popular thermal or mechanical nociception tests. When tissue-type plasminogen activator (tPA) was injected 6 h after the PIT stress, tPA-dependent hypersensitivity to the electrical paw stimulation and stable thermal and mechanical hyperalgesia on both sides for more than 17 or 18 days after the PIT treatment. These hyperalgesic effects were abolished in lysophosphatidic acid receptor 1 (LPA1)- and lysophosphatidic acid receptor 3 (LPA3)-deficient mice. When Ki-16425, an LPA1 and LPA3 antagonist was treated twice daily for 6 days consecutively, the thermal and mechanical hyperalgesia at day 17 and 18 were significantly reversed. The liquid chromatography–mass spectrometry (LC–MS/MS) analysis revealed that there is a significant increase in several species of LPA molecules in somatosensory S-I and medial dorsal thalamus (MD), but not in striatum or ventroposterior thalamus. All these results suggest that LPA1 and LPA3 signaling play key roles in the development and maintenance of CPSP.

The Spectrum of Glomerulopathies in Kashmir: A Tertiary Care Experience

Background: There is a paucity of data on the spectrum of renal diseases prevalent in the Jammu and Kashmir region. Objectives: To determine the spectrum of glomerulopathies in adult patients attending a tertiary care centre. Methods: Two hundred and twenty-one adequate biopsies from native kidneys of adult patients who presented with features suggestive of glomerular diseases at Sheri Kashmir Institute of medical sciences Srinagar Kashmir for the last 8 years were studied in a retrospective manner. Light and immunofluorescence (IF) microscopy were performed to evaluate these biopsies after obtaining well-informed consent from each patient. Results: Of the 221 biopsies carried out, 150 were performed on males and 71 on females with the mean age of 29 ± 13.5 years. The main presentation was the nephrotic syndrome in 177 (80%), hypertension in 60 (27%), renal insufficiency in 48 (21.7%), and abnormal urinary sediment in 42 (20.3%) of patients. The histopathology revealed minimal change disease (MCD) in 69 (31.2%), membranous glomerulonephritis (MGN) in 48 (21.7%), focal segmental glomerulsclerosis (FSG) in 49 (18%), and mesangioproliferative glomerulonephritis in 16 (7.2%). Patients with atypical presentation of diabetes mellitus showed diabetic nephropathy in 12 (5.4%) patients. Lupus nephritis was in 5 (2.2%) patients. Majority of the patients with MPGN had Immunoglobulin A deposits on IF. While evaluating the underlying cause of MGN, only 1 patient, a 62-year-old male, proved to have adenocarcinoma of the stomach. In the remaining patients, no secondary cause could be found. Thrombotic complications seen in our study were deep venous thrombosis, renal vein thrombosis and middle cerebral artery thrombosis. Conclusion: MCD and MGN were the most common primary glomerular diseases observed in our centre.

Intrauterine Bilateral Upper Limb Gangrene and Cerebral Infarction in Preterm Infant: A Case Report and Literature Review

Intrauterine limb gangrene with cerebral infarction is a rare condition and only few cases of this condition have been reported. The neonatal thrombosis needs to be distinguished from intrauterine arterial thrombosis as it is caused by catheterization of the umbilical artery or less commonly seen as complication of sepsis or coagulation disorders. The report describes the case of preterm infant with bilateral brachial artery thrombosis in utero and neonatal gangrene of the left forearm. The right forearm of the infant had a small patch of gangrene with irregular areas of edema and bluish discoloration, extending to the hand. The hand of infant was associated with thrombosis of left middle cerebral artery and acute infarction in left cerebral hemisphere. Both of the upper limbs in the patient were affected, including the left cerebral hemisphere; although in majority of the cases, the limbs are equally affected and the left side of the brain is preferentially involved. LMWH was administered in the present case, which significantly improved the upper right limb. Laboratory findings, including the coagulation markers within normal reference, ranges for the chronologic and gestational age. Further complications were prevented by early post-natal use of anticoagulants and prevention of infection; although the exact cause of this condition was not clear.

Prasugrel reduces ischaemic infarct volume and ameliorates neurological deficits in a non-human primate model of middle cerebral artery thrombosis

Several clinical trials have demonstrated the benefits of thienopyridine monotherapy in ischaemic stroke patients. Non-human primate models of ischaemic stroke have been used for various antithrombotic agents; however, to the best of our knowledge, there is no data on the effects of P2Y12 antagonists in models, such as the thrombotic middle cerebral artery occlusion (MCAO) monkey model. Accordingly, it remains unclear what level of inhibition of platelet aggregation (IPA) is required for optimal treatment of ischaemic stroke. In the present study, we investigated the effects of prasugrel, a third-generation thienopyridine antiplatelet drug, on platelet aggregation, thrombus formation and cerebral infarct volume in a non-human primate model. Daily oral administration of prasugrel resulted in significant and stable platelet inhibitory effects on Day 3, with IPA values ranging from 31% to 36% at 0.3mg/kg/day and from 44% to 50% at 1mg/kg/day. These IPA levels encompassed values observed in clinical trials of clopidogrel, and were thus selected for further study. In the thrombotic MCAO model, prasugrel increased MCA patency in a dose-dependent manner and significantly reduced ischaemic infarct volume by approximately 70% at 0.3mg/kg/day and 90% at 1mg/kg/day without increasing haemorrhagic infarction. Prasugrel also significantly reduced neurological deficit scores by 60% at 0.3mg/kg/day and 80% at 1mg/kg/day. In conclusion, prasugrel treatment resulted in effective reduction of ischaemic infarction and an associated improvement in neurological function without increasing haemorrhagic infarction. These data suggest that prasugrel monotherapy would be effective for the prevention of thrombotic stroke.

Reperfusion of cerebral artery thrombosis by the GPIb–VWF blockade with the Nanobody ALX-0081 reduces brain infarct size in guinea pigs

AbstractThrombolytic therapy is the cornerstone of treatment of acute atherothrombotic ischemic stroke but is associated with brain hemorrhage; antiplatelet therapy has limited efficacy and is still associated with intracranial bleeding. Therefore, new antithrombotic approaches with a better efficacy/safety ratio are required. We have assessed the effect of ALX-0081, a Nanobody against the A1 domain of von Willebrand factor (VWF) that blocks VWF binding to GPIb, of the thrombolytic agent recombinant tissue plasminogen activator (rtPA), and of the GPIIb/IIIa antagonist tirofiban, in a middle cerebral artery (MCA) thrombosis model in guinea pigs. Drugs were administered before, immediately after, or 15 or 60 minutes after the total occlusion of the MCA. ALX-0081 prevented MCA thrombosis and induced reperfusion when given immediately after and 15 minutes after complete occlusion and reduced brain damage without inducing hemorrhage, whereas tirofiban prevented thrombosis but did not induce reperfusion and induced striking brain hemorrhage. rtPA also induced reperfusion when given 60 minutes after occlusion but provoked brain hemorrhage. Skin bleeding time was not modified or was moderately prolonged by ALX-0081, whereas tirofiban and rtPA prolonged it. The inhibition of the GPIb–VWF axis in guinea pigs prevents cerebral artery thrombosis and induces early reperfusion without provoking intracerebral bleeding thus reducing brain infarct area.