Treatment of ChAdOx1 nCoV-19 Vaccine-Induced Immune Thrombotic Thrombocytopenia Related Acute Ischemic Stroke.

Recently cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) and thrombosis following the adenoviral vector vaccine against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were reported. A mechanism similar to heparin-induced thrombocytopenia was proposed with antibodies to platelet factor 4 (PF4). Vaccine related arterial thrombosis in the brain is rare but life-threatening and optimal treatment is not established. We report clinical, laboratory, imaging findings and treatment in a 51-year-old female presenting with acute left middle cerebral artery (MCA) occlusion 7 days after the first dose of ChAdOx1 nCoV-19 vaccine. Due to low platelet count and suspicion of VITT she was not eligible for intravenous thrombolysis (IVT) and proceeded to mechanical thrombectomy (MER) with successful recanalization four hours after onset of symptoms. Treatment with intravenous immunoglobulin (IVIG) and heparin pentasaccharide fondaparinux was initiated. Presence of anti-PF4 antibodies was confirmed. The patient improved clinically with normalization of platelet count. Clinicians should be alert of VITT in patients with acute ischemic stroke after ChAdOx1 nCov-19 vaccination and low platelet counts. MER showed to be feasible and effective. We propose considering MER in patients with VITT and large vessel occlusion despite thrombocytopenia. High-dose IVIG should be started immediately. Alternative anticoagulation to heparin should be started 24 hours after stroke onset unless significant hemorrhagic transformation occurred. Platelet transfusion is contraindicated and should be considered only in severe hemorrhagic complications. Restenosis or reocclusion of the revascularized artery is possible due to the hypercoagulable state in VITT and angiographic surveillance after the procedure is reasonable.

In vivo imaging of Α7 nicotinic receptors as a novel method to monitor neuroinflammation after cerebral ischemia.

In vivo positron emission tomography (PET) imaging of nicotinic acetylcholine receptors (nAChRs) is a promising tool for the imaging evaluation of neurologic and neurodegenerative diseases. However, the role of α7 nAChRs after brain diseases such as cerebral ischemia and its involvement in inflammatory reaction is still largely unknown. In vivo and ex vivo evaluation of α7 nAChRs expression after transient middle cerebral artery occlusion (MCAO) was carried out using PET imaging with [11 C]NS14492 and immunohistochemistry (IHC). Pharmacological activation of α7 receptors was evaluated with magnetic resonance imaging (MRI), [18 F]DPA-714 PET, IHC, real time polymerase chain reaction (qPCR) and neurofunctional studies. In the ischemic territory, [11 C]NS14492 signal and IHC showed an expression increase of α7 receptors in microglia and astrocytes after cerebral ischemia. The role played by α7 receptors on neuroinflammation was supported by the decrease of [18 F]DPA-714 binding in ischemic rats treated with the α7 agonist PHA 568487 at day 7 after MCAO. Moreover, compared with non-treated MCAO rats, PHA-treated ischemic rats showed a significant reduction of the cerebral infarct volumes and an improvement of the neurologic outcome. PHA treatment significantly reduced the expression of leukocyte infiltration molecules in MCAO rats and in endothelial cells after in vitro ischemia. Despite that, the activation of α7 nAChR had no influence to the blood brain barrier (BBB) permeability measured by MRI. Taken together, these results suggest that the nicotinic α7 nAChRs play a key role in the inflammatory reaction and the leukocyte recruitment following cerebral ischemia in rats.

Netrin-1 attenuates brain injury after middle cerebral artery occlusion via downregulation of astrocyte activation in mice.

BACKGROUND: Netrin-1 functions largely via combined receptors and downstream effectors. Evidence has shown that astrocytes express netrin-1 receptors, including DCC and UNC5H2. However, whether netrin-1 influences the function of astrocytes was previously unknown. METHODS: Lipopolysaccharide was used to stimulate the primary cultured astrocytes; interleukin release was used to track astrocyte activation. In vivo, shRNA and netrin-1 protein were injected in the mouse brain. Infarct volume, astrocyte activation, and interleukin release were used to observe the function of netrin-1 in neuroinflammation and brain injury after middle cerebral artery occlusion. RESULTS: Our results demonstrated that netrin-1 reduced lipopolysaccharide-induced interleukin-1ß and interleukin-12ß release in cultured astrocytes, and blockade of the UNC5H2 receptor with an antibody reversed this effect. Additionally, netrin-1 increased p-AKT and PPAR-γ expression in primary cultured astrocytes. In vivo studies showed that knockdown of netrin-1 increased astrocyte activation in the mouse brain after middle cerebral artery occlusion (p < 0.05). Moreover, injection of netrin-1 attenuated GFAP expression (netrin-1 0.27 ± 0.06 vs. BSA 0.62 ± 0.04, p < 0.001) and the release of interleukins and reduced infarct volume after brain ischemia (netrin-1 0.27 ± 0.06 vs. BSA 0.62 ± 0.04 mm3, p < 0.05). CONCLUSION: Our results indicate that netrin-1 is an important molecule in regulating astrocyte activation and neuroinflammation in cerebral ischemia and provides a potential target for ischemic stroke therapy.

Role of astrocyte activation in fine particulate matter-enhancement of existing ischemic stroke in Sprague-Dawley male rats.

Exposure to particulate matter (PM) with an aerodynamic diameter of less than 2.5 µm (PM2.5) is associated with increased risk of ischemic stroke, but potential neurotoxic mechanisms remain to be determined. In this study, adult male Sprague- Dawley (SD) rats were divided into four groups as follows: control (CON), PM2.5 exposure (PM alone), ischemic stroke (IS), and ischemic stroke and PM2.5 (IS-PM). Ischemic stroke groups were prepared by middle cerebral artery occlusion (MCAO), and neurobehavior was assessed daily for 7 consecutive days. The control group was administered intranasally 20 µl PBS, while PM2.5 alone was given as 20 µl of PM2.5 (10 mg/ml) intranasal daily for 7 consecutive days. The spontaneous locomotion and exploratory behavior of rats were assessed by the open field test. Cells positive for glial fibrillary acidic protein (GFAP) and inducible nitric oxide synthase (iNOS) were determined for astrocyte activation and inflammatory reactions. Neuronal edema and pyknosis in the cerebral cortex, hippocampus, and midbrain were observed in IS groups with or without PM2.5 treatment. Astrocyte activity was enhanced, whereas spontaneous locomotion and exploratory movements decreased in the IS-PM group. Data demonstrated that astrocytes activation and inflammatory reactions may play a role in IS and that exposure to PM2.5 may aggravate the neurobehavioral alterations observed in rats suffering from IS.

Acute Antero-Inferior Wall Ischaemia with Acute Ischaemic Stroke Caused by Oral Ingestion of Cannabis in a Young Male.

Cannabis is a frequently used illicit recreational drug that is known to be associated with a variety of psychopharmacological effects. Negative somatic effects such as myocardial infarction and stroke have been reported, though, less frequently. Most of the literature available has focused on the complications due to smoked forms of cannabis (ganja and charas). Here we report a case of acute myocardial ischaemia with acute ischaemic stroke developing after oral ingestion of 'Bhang', a preparation of cannabis.

[Tripotolide ameliorates inflammation and apoptosis induced by focal cerebral ischemia/reperfusion in rats].

Objective: To investigate the effects of triptolide on inflammation and apoptosis induced by focal cerebral ischemia/reperfusion in rats. Methods: The rat model of focal cerebral ischemia/reperfusion injury was established according to Longa's method. A total of 80 SD rats were randomly divided into 5 groups:normal control, sham group, DMSO group, middle cerebral artery occlusion (MCAO) group, and MCAO with tripolide treatment group. TTC staining was used to examine the site and volume of cerebral infarction, and Longa score was employed for neurological disorders measurement. Number of astrocytes was measured by fluorescence staining, and neuronal apoptosis was determined by TUNEL staining. The expressions of inducible nitric oxide synthase(iNOS), cyclooxygenase 2(COX-2) and NF-κB proteins were detected by immunohistochemistry, and the expression of iNOS, COX-2 mRNA was detected by real-time PCR. Results: Compared with DMSO group and MCAO group, brain edema was improved (80.03±0.46)% (P<0.05), infarct volume was reduced (8.3±1.4)% (P<0.01), Longa score was decreased (1.38±0.20, P<0.05) in triptolide treatment group. Meanwhile triptolide also dramatically reduced the number of GFAP-positive astrocytes (P<0.05), alleviated protein expression of COX-2 (91.67±1.31), iNOS (95.24±5.07) and NF-κB (75.03±2.06) triggered by MCAO (all P<0.05), and induced a down-regulation of cell apoptosis as showed by TUNEL assay (64.15±3.52, P<0.05). Conclusion: Triptolide can reduce the cerebral infarction volume, attenuate brain edema and ameliorate the neurological deficits induced by cerebral ischemia-reperfusion injury rats, indicating that it might be used as a potential anti-inflammatory agent.

Effects of a TAFI-inhibitor combined with a suboptimal dose of rtPA in a murine thromboembolic model of stroke.

BACKGROUND: Since thrombolysis is the only approved intervention for ischemic stroke, improving its efficacy and safety is a therapeutic aim of considerable interest. The activated form of thrombin activatable fibrinolysis inhibitor (TAFI) has antifibrinolytic effects, and inhibition of TAFI might thus favor recanalization. The present study compared efficacy between TAFI inhibition alone and TAFI inhibition in combination with rtPA at a suboptimal dose, in a murine model of thromboembolic stroke. METHODS: Focal ischemia was induced in mice by thrombin injection in the middle cerebral artery. Animals were placed within the magnet immediately after surgery for baseline MRI (H0). MRI examination comprised diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), and T2-weighted imaging (T2-WI). Animals were randomly assigned to 1 of 5 treatment groups: saline, rtPA 5 mg/kg (tPA(5): suboptimal or low dose), rtPA 10 mg/kg (tPA(10): standard dose), TAFI-I 100 mg/kg (TAFI-I), and rtPA 5 mg/kg + TAFI-I 100 mg/kg (tPA(5) + TAFI-I). Treatments were administered inside the magnet, via a catheter placed in the tail vein, using a power injector, as 10% bolus and 90% infusion over a period of 20 min. MRI examination was repeated at 3 h (H3) and 24 h (H24) after surgery. Therapeutic benefit was evaluated by: (1) improvement of reperfusion and (2) reduction in final lesion size. Microhemorrhages were assessed as black spots on T2-WI at H24. Animals were sacrificed after the last MR examination. The surgeon and all investigators were blinded to treatment allocation. RESULTS: A total of 104 mice were operated on. Forty four of these were excluded from the study and 27 from the analysis, according to a priori defined criteria (no lesion or no mismatch), leading to the following distribution: saline (n = 6), tPA(5) (n = 8), tPA(10) (n = 7), TAFI-I (n = 7), and TAFI-I + tPA(5) (n = 5). Standard-dose rtPA treatment (tPA(10)) significantly improved lesion regression between H0 and H24 compared to saline (-57 ± 18% vs. -36 ± 21%, p = 0.03), which treatment with rtPA(5) or TAFI-I alone did not. On the other hand, combined treatment with tPA(5) + TAFI-I showed only a trend toward lesion regression (-49 ± 26%), similarly to treatment with tPA(10), but not significantly different from saline (p = 0.46). Nine animals showed microhemorrhage on T2-WI at H24. These animals were evenly distributed between groups. CONCLUSIONS: The present study showed that the combination of TAFI-I with a suboptimal dose of rtPA is not as effective as the standard dose of rtPA, while TAFI inhibition alone is not effective at all. The thromboembolic model is of particular interest in assessing rtPA association to improve thrombolysis, especially when coupled with longitudinal MRI assessment.

Severe visual loss and cerebral infarction after injection of hyaluronic acid gel.

We report a case of a 23-year-old man with cerebral infarction and permanent visual loss after injection of a hyaluronic acid gel filler for augmentation rhinoplasty. The patient was admitted to the hospital with complaints of loss of vision in the right eye, facial paralysis on the right side, and paralysis of the left limbs with severe pain during augmentation rhinoplasty with filler injection. Brain magnetic resonance imaging and computed tomography showed ophthalmic artery obstruction and right middle cerebral artery infarction. Acute thrombolysis was performed to treat the infarction; however, the patient's condition did not improve. Intracerebral hemorrhage in the right temporal/frontal/occipital/parietal lobe, subarachnoid hemorrhage, and midline shifting were observed on brain computed tomography after 24 hours after thrombolysis. Emergency decompressive craniectomy was performed. After the surgery, the patient continued to experience drowsiness, with no improvement in visual loss and motor weakness. Three months later, he could walk with cane. This case indicates that surgeons who administer filler injections should be familiar with the possibility of accidental intravascular injection and should explain the adverse effects of fillers to patients before surgery.

Synthetic cannabis and acute ischemic stroke.

An association between marijuana use and stroke has been previously reported. However, the health risks of newer synthetic cannabinoid compounds are less well known. We describe 2 cases that introduce a previously unreported association between synthetic cannabis use and ischemic stroke in young adults. A 22-year-old woman presented with dysarthria, left hemiplegia, and left hemianesthesia within hours of first use of synthetic cannabis. She was healthy and without identified stroke risk factors other than oral contraceptive use and a patent foramen ovale without venous thromboses. A 26-year-old woman presented with nonfluent aphasia, left facial droop, and left hemianesthesia approximately 12 hours after first use of synthetic cannabis. Her other stroke risk factors included migraine with aura, oral contraceptive use, smoking, and a family history of superficial thrombophlebitis. Both women were found to have acute, large-territory infarctions of the right middle cerebral artery. Our 2 cases had risk factors for ischemic stroke but were otherwise young and healthy and the onset of their deficits occurred within hours after first-time exposure to synthetic cannabis. Synthetic cannabis use is an important consideration in the investigation of stroke in young adults.

Alpha 1-antitrypsin therapy mitigated ischemic stroke damage in rats.

Our objective is to develop a new therapy for the treatment of stroke. Currently, the only effective therapy for acute ischemic stroke is the thrombolytic agent recombinant tissue plasminogen activator. α1-Antitrypsin (AAT), a serine proteinase inhibitor with potent anti-inflammatory, anti-apoptotic, antimicrobial, and cytoprotective activities, could be beneficial in stroke. The goal of this study is to test whether AAT can improve ischemic stroke outcome in an established rat model. Middle cerebral artery occlusion was induced in male rats via intracranial (i.c.) microinjection of endothelin-1. Five to 10 minutes after stroke induction, rats received either i.c. or intravenous delivery of human AAT. Cylinder and vibrissae tests were used to evaluate sensorimotor function before and 72 hours after middle cerebral artery occlusion. Infarct volumes were examined via either 2,3,5-triphenyltetrazolium chloride assay or magnetic resonance imaging 72 hours after middle cerebral artery occlusion. Despite equivalent initial strokes, at 72 hours, the infarct volumes of the human AAT treatment groups (local and systemic injection) were statistically significantly reduced by 83% and 63% (P < .0001 and P < .05, respectively) compared with control rats. Human AAT significantly limited sensory motor system deficits. Human AAT could be a potential novel therapeutic drug for the protection against neurodegeneration after ischemic stroke, but more studies are needed to investigate the protective mechanisms and efficacy in other animal models.

Cannabis-related myocardial infarction and cardioembolic stroke.

We report a 33-year-old man with a history of chronic cannabis use who sustained myocardial infarction followed by cerebral infarction after a recent significant increase in cannabis use. This is the first case of cannabis-associated stroke of probable cardioembolic origin.

Cerebroprotection by angiotensin-(1-7) in endothelin-1-induced ischaemic stroke.

Activation of angiotensin-converting enzyme 2 (ACE2), production of angiotensin-(1-7) [Ang-(1-7)] and stimulation of the Ang-(1-7) receptor Mas exert beneficial actions in various peripheral cardiovascular diseases, largely through opposition of the deleterious effects of angiotensin II via its type 1 receptor. Here we considered the possibility that Ang-(1-7) may exert beneficial effects against CNS damage and neurological deficits produced by cerebral ischaemic stroke. We determined the effects of central administration of Ang-(1-7) or pharmacological activation of ACE2 on the cerebral damage and behavioural deficits elicited by endothelin-1 (ET-1)-induced middle cerebral artery occlusion (MCAO), a model of cerebral ischaemia. The results of the present study demonstrated that intracerebroventricular infusion of either Ang-(1-7) or an ACE2 activator, diminazine aceturate (DIZE), prior to and following ET-1-induced MCAO significantly attenuated the cerebral infarct size and neurological deficits measured 72 h after the insult. These beneficial actions of Ang-(1-7) and DIZE were reversed by co-intracerebroventricular administration of the Mas receptor inhibitor, A-779. Neither the Ang-(1-7) nor the DIZE treatments altered the reduction in cerebral blood flow elicited by ET-1. Lastly, intracerebroventricular administration of Ang-(1-7) significantly reduced the increase in inducible nitric oxide synthase mRNA expression within the cerebral infarct that occurs following ET-1-induced MCAO. This is the first demonstration of cerebroprotective properties of the ACE2-Ang-(1-7)-Mas axis during ischaemic stroke, and suggests that the mechanism of the Ang-(1-7) protective action includes blunting of inducible nitric oxide synthase expression.

Halogenated aromatic amino acid 3,5-dibromo-D: -tyrosine produces beneficial effects in experimental stroke and seizures.

The effects of the halogenated aromatic amino acid 3,5-dibromo-D: -tyrosine (3,5-DBr-D: -Tyr) were studied in rat models of stroke and epileptic seizures caused by middle cerebral artery occlusion (MCAo) through respective intracerebral injection of endothelin-1 (ET-1) and intraperitoneal (i.p.) injection of pentylenetetrazole (PTZ). 3,5-DBr-D: -Tyr was administered as three bolus injections (30 or 90 mg/kg, i.p.) starting at 30, 90, and 180 min after ET-1 administration or as a single bolus (30 mg/kg, i.p.) 15 min prior to PTZ administration. Neurological deficits and infarct volume were estimated 3 days after ET-1 administration and seizure score was assessed during the first 20 min after PTZ administration. The safety of 3,5-DBr-D: -Tyr was evaluated in control animals using telemetry to measure cardiovascular parameters and immunostaining to assess the level of activated caspase-3. 3,5-DBr-D: -Tyr significantly improved neurological function and reduced infarct volume in the brain even when the treatment was initiated 3 h after the onset of MCAo. 3,5-DBr-D: -Tyr significantly depressed PTZ-induced seizures. 3,5-DBr-D: -Tyr did not cause significant changes in arterial blood pressure, heart rate and spontaneous locomotor activity, nor did it increase the number of activated caspase-3 positive cells in the brain. We conclude that 3,5-DBr-D: -Tyr, by alleviating the deleterious effects of MCAo and PTZ in rats with no obvious intrinsic effects on cardiovascular parameters and neurodegeneration, exhibits promising potential as a novel therapeutic direction for stroke and seizures.

Embolic Stroke Model with Magnetic Nanoparticles.

Stroke models are vital tools in neuropharmacology and rehabilitation research. However, a classic and widely used model-the suture occlusion model-is not suitable for all research approaches, especially regarding thrombolysis. For embolic stroke models in thrombolytic research, the surgical procedures of thrombin injection in the middle cerebral artery or clot injection in the carotid artery involved are too sophisticated. Here, we report a new stroke model in mice that uses magnetic nanoparticle (MNP) cross-linked with thrombin to embolize. Briefly, after the magnet was positioned in the common carotid artery, MNP@Thrombin was injected from the tail vein. Within several minutes postinjection, the MNP@Thrombin accumulated in the carotid artery and induced thrombus formation. These complex clots were flushed into and subsequently blocked the cerebral artery. Collectively, these results suggested that this new method was a quick and easy stroke model that blocked hemisphere blood flow and damaged neural function. Importantly, this model had an excellent response to thrombolytic drugs. After urokinase injection, cerebral blood flow was restored and symptom scores were enhanced by nearly one. This method, including a quick synthesis of MNP and thrombin, provided an easy and minimally invasive process for a new stroke model that is usable in both pharmacological and rehabilitative research.

TET3 regulates DNA hydroxymethylation of neuroprotective genes following focal ischemia.

The 5-hydroxymethylcytosine (5hmC) epigenetic modification is highly enriched in the CNS and a critical modulator of neuronal function and development. We found that cortical 5hmC was enhanced from 5 min to three days of reperfusion following focal ischemia in adult mice. Blockade of the 5hmC-producing enzyme ten-eleven translocase 3 (TET3) increased edema, infarct volume, and motor function impairments. To determine the mechanism by which TET3 provides ischemic neuroprotection, we assessed the genomic regions where TET3 modulates 5hmC. Genome-wide sequencing analysis of differentially hydroxymethylated regions (DhMRs) revealed that focal ischemia robustly increased 5hmC at the promoters of thousands of genes in a TET3-dependent manner. TET3 inhibition reduced 5hmC at the promoters of neuroprotective genes involved in cell survival, angiogenesis, neurogenesis, antioxidant defense, DNA repair, and metabolism demonstrating a role for TET3 in endogenous protection against stroke. The mRNA expression of several genes with known involvement in ischemic neuroprotection were also reduced with TET3 knockdown in both male and female mice, establishing a correlation between decreased promoter 5hmC levels and decreased gene expression. Collectively, our results indicate that TET3 globally increases 5hmC at regulatory regions and overwhelmingly modulates 5hmC in several neuroprotective pathways that may improve outcome after ischemic injury.

Intravenous tissue plasminogen activator thrombolysis in patients without major arterial occlusion seems to be safe and effective.

BACKGROUND: It is not clear whether tissue plasminogen activator (t-PA) thrombolysis in patients without major arterial occlusion is effective or safe. METHODS: Consecutive anterior circulation stroke patients treated with t-PA within 3 h of onset were studied. The patients were divided into three groups according to magnetic resonance angiography findings before t-PA infusion: ICA group, ICA occlusion; MCA group, M1 and M2 occlusion, and no occlusion group. Clinical characteristics, the presence of hemorrhagic transformation on T2* at 24 h after t-PA thrombolysis, and outcome at 3 months were compared among the three groups. RESULTS: 112 patients were enrolled. The no occlusion group had 21 (18.8%) patients, the ICA group had 29 (25.9%), and the MCA group had 62 (55.4%). The frequency of hemorrhagic transformation was only 4.8% in the no occlusion group (31.0% for the ICA group, and 48.4% for the MCA group, p = 0.0012). At 3 months after t-PA therapy, 61.5% of the no occlusion group had a favorable outcome (modified Rankin score 0-1), which was the highest among the three groups (15.0% for the ICA group, and 41.5% for the MCA group, p = 0.0203). CONCLUSION: Intravenous t-PA therapy in acute stroke patients without major artery occlusion seems to be safe and effective.

Pinocembrin protects the neurovascular unit by reducing inflammation and extracellular proteolysis in MCAO rats.

The purpose of the present study was to examine the protective action and mechanisms of pinocembrin (1) on the neurovascular unit (NVU) in permanent cerebral ischemic rats. Focal cerebral ischemia was induced by occlusion of middle cerebral artery (MCAO) in rats. Compound 1 (3, 10, or 30 mg/kg) was intravenously injected at 0, 8, 16 h after MCAO. At 24 h of occlusion, 1 alleviated neuronal apoptosis, edema of astrocytic end-feet, and the deformation of endothelial cells and capillaries as revealed by the transmission electron microscopy study. To understand the mechanisms of action, the anti-inflammation effect of 1 was examined. Compound 1 reduced the expressions of tumor necrosis factor-alpha, interleukin-1beta, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, inducible NO synthase and aquaporin-4; inhibited the activation of microglias and astrocytes; and downregulated the expression of matrix metalloproteinases (MMPs) in the ischemic brain. The ischemia-induced decreases in mRNA expressions of tight junction constituent proteins, occludin and ZO-1, were also inhibited by 1. These results indicated that 1 can protect the rat brain against ischemia injury by inhibiting the inflammatory cascade, reducing the expression of MMP-9, and preventing the integrity of tight junction. This resulted in the protective action of 1 on the NVU.

[Cannabis-induced cerebral and myocardial infarction in a young woman]. / Infarctus cérébral et myocardique après consommation de cannabis chez une femme jeune.

INTRODUCTION: Cannabis is the most consumed drug in the world particularly in young adults. Few reports have suggested a causal role of cannabis in the development of cerebral or cardiovascular events. We describe the first association of myocardial infarction and stroke after heavy cannabis consumption in a 45-year-old woman. OBSERVATION: Stroke occurred in relation with a right carotid and middle cerebral artery thrombosis after cannabis abuse. The patient was successfully treated with intravenous rt-PA. Two days after her admission, she presented a myocardial infarction due to a coronary thrombosis. Cerebral and coronary arteries were angiographically normal. Etiological tests were negative and a toxic cause in relation with cannabis consumption was concluded. CONCLUSION: Cannabis can be associated with vascular events by different mechanisms. Thrombosis may occur in cerebral and/or coronary arteries. We suggest that it might be useful to search for cannabis consumption systematically in young subjects victims of stroke and myocardial infarction.

Neuroprotective effect of low-intensity transcranial ultrasound stimulation in endothelin-1-induced middle cerebral artery occlusion in rats.

BACKGROUND: Ischemic stroke is one of the leading causes of death and disability worldwide. Low-intensity transcranial ultrasound stimulation (LITUS) is a promising neuroprotective treatment for ischemic stroke. Diffusion-weighted imaging (DWI) can be highly sensitive in the detection of ischemic brain injury. Relative apparent diffusion coefficient (rADC) values can be used to evaluate the effect of LITUS on ischemic stroke. PURPOSE: The aim of this study was to determine the neuroprotective effect of LITUS at different time points using endothelin-1-induced middle cerebral artery occlusion in rats as a model of ischemic stroke. METHODS: Endothelin-1 (ET-1) was injected into the cerebral parenchyma near the middle cerebral artery, which induced focal, reversible, low-flow ischemia in rats. After occlusion of the middle cerebral artery for 30 min, 120 min, and 240 min, LITUS stimulation was used respectively. DWI was performed at 1, 3, 6, 12, 18, 24, 48, and 72 h after ischemia using a 3 T scanner. The rADC values were calculated, and functional outcomes assessed using neurobehavioral scores after ischemia. Nissl staining and estimation of Na+-K+-ATPase activity were used to assess the neuropathology after completing the last Magnetic Resonance Imaging (MRI) examination. RESULTS: Endothelin-1-induced occlusion of the middle cerebral artery resulted in significant dysfunction and neuronal damage in rats. Rats that received LITUS exhibited reduced damage of the affected brain tissue after cerebral ischemia. The greatest protective effect was found when LITUS stimulation occurred 30 min after cerebral ischemia. CONCLUSIONS: Imaging, behavioral, and histological results suggested that LITUS stimulation after an ischemic stroke produced significant neuroprotective effects.

Motor deficit in the mouse ferric chloride-induced distal middle cerebral artery occlusion model of stroke.

Ferric chloride-induced distal middle cerebral artery occlusion (MCAO) model of stroke was described in mice several years ago, however it lacked in-depth evaluation of the post-stroke functional outcomes in the animals. In this study, we reproduced the recently developed model and expanded its characterization by thorough evaluation of blood supply, cerebral infarction, and motor function in adult male and female mice up to 14 days after stroke. Our observations indicate near complete interruption of blood flow in the distal MCA shortly after application of 20 % ferric chloride over the artery through a cranial window, which remained occluded for at least 4 h. As expected, infarction of the brain tissue, documented by TTC and hematoxylin stains, was restricted to the cerebral cortex. We also systematically evaluated motor impairment of the animals in this model. For this, a series of studies were carried out in male and female mice up to 14 days after stroke, and motor function was assessed in cylinder and grid-walking tests in blinded manner. Contrary to our expectations, the results of both motor tests indicated minor, transient motor deficit in mice after stroke. Based on these observations, we conclude that the mouse ferric chloride-induced distal MCAO model is likely not suitable for proof-of-concept and preclinical studies where motor function is an important outcome measure.