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A Shuaib

Publications and source records attributed to A Shuaib.

At least 37 records · Page 2Linked to original sources
PubMed2000

Dose-dependent neuroprotection with tiagabine in a focal cerebral ischemia model in rat.

Enhancement of the inhibitory activity of GABA may protect ischemic neurons. We evaluated the neuroprotective effect of tiagabine, a novel GABA agonist, in reversible focal cerebral ischemia rats subjected to 2h middle cerebral artery (MCA) occlusion. Tiagabine was given at 10, 20 and 40 mg/kg, i.p., 2 h after the onset of reperfusion. We found that post-ischemia treatment with tiagabine improved neurobehavioral outcome and reduced brain infarction volume in a dose-dependent manner. The data suggest that post-ischemic administration of tiagabine is neuroprotective in the focal cerebral ischemia model.

Animals↗
PubMed2000

Return of stuttering after stroke.

The pathophysiology of developmental or acquired stuttering still remains an enigma. In a few cases, the developmental stuttering that had disappeared spontaneously or as a result of therapy reoccurred following a brain lesion. We report on a patient with return of developmental stuttering following a left hemispheric stroke. This case supports the theory that acquired brain lesions may cause a return of stuttering, possibly by interfering with the compensatory mechanism(s) that once had relieved the developmental stuttering.

Aged↗
PubMed2000

Evaluation of an optimal temperature for brain storage in delayed 2, 3,5-triphenyltetrazolium chloride staining.

This paper presents the determination of an optimal temperature for delayed 2,3,5-triphenyltetrazolium chloride (TTC) staining. Twenty-one rats were subjected to right middle cerebral artery embolic stroke and sacrificed 96 h following ischemia. The brains were harvested and stained immediately after sacrifice or stored for 8 h at 21-23 degrees C or 4 degrees C, respectively. The stained sections were scanned and infarct volume calculated. The quality of staining, distinction of borders between infarcted and non-ischemic tissue and ease of differentiating ischemic tissue in colored and grayscale images was assessed. The present study indicates that results of TTC obtained immediately after animal sacrifice, or delayed TTC staining while storing the brains at room temperature or 4 degrees C are comparable.

Animals↗
PubMed2000

Survival and histological evaluation of therapeutic window of post-ischemia treatment with magnesium sulfate in embolic stroke model of rat.

The neuroprotective window of magnesium for up to 8 h after ischemic insult was evaluated in a clinically relevant model of focal cerebral ischemia subjected to embolization of the right middle cerebral artery (MCA) with an autologous thrombus. The animals were treated with either vehicle or 5% magnesium sulfate (90 mg/kg) intravenously at 2, or 6, or 8 h after ischemic insult. Survival rate significantly increased only in animals treated with magnesium sulfate in treatment groups at 2 h after MCA embolization but improvement in neurological outcome was observed in all medicated groups. Compared with animals in control group, post-ischemia treatment with magnesium sulfate significantly reduced brain infarct volume (P<0.01) except the 8 h group. These data indicate that the therapeutic window for neuroprotection of magnesium can be extended up to 6 h in the focal cerebral ischemia model of this study. The long window of opportunity for effective dosing may be explained with the proposed multiple mechanisms of actions for magnesium.

Animals↗
PubMed2000

Enhanced neuroprotection and reduced hemorrhagic incidence in focal cerebral ischemia of rat by low dose combination therapy of urokinase and topiramate.

Thrombolysis is increasingly being used in treating acute ischemic stroke but it is also accompanied with a serious complication of cerebral hemorrhage in a dose-dependent fashion. As a lower dose may result in decreased effectiveness, we tested the efficacy of combining a neuroprotective agent, topiramate (TPM), with lower doses of intra-arterial urokinase in an embolic stroke model. Focal ischemia was produced by introduction of an autogenous thrombus into the right middle cerebral artery. Urokinase was infused via the ipsilateral internal carotid artery and neuroprotective agent, TPM, was administrated intra-peritoneally 2 h following ischemic insult. The animals were assigned to five groups: (1) control group (n=6); (2) urokinase 5000 units/kg (n=8); (3) urokinase at 2500 units/kg (n=8); (4) topiramate at 20 mg/kg (n=8); (5) urokinase at 2500 units/kg and topiramate at 20 mg/kg (n=8). Neurobehavioral outcome and the degree of brain infarct volume were assessed at 24 h. Three animals in the group treated by high dose urokinase developed intracranial hemorrhage but none in other groups. Animals in all medication-groups showed significant improvement in neurobehavioral score. Post-ischemia treatment with urokinase or TPM alone significantly attenuated brain infarct volume (low-dose urokinase, 39.1+/-13.0%, p<0.05; high-dose, 18.4+/-8.5%, p<0.001; TPM, 20. 1+/-11.2%, p<0.001) when compared to the control (54.2+/-9.04%). Addition of TPM to low dose urokinase achieved better neuroprotection (8.2+/-6.0%) than any single-drug-treated groups. Our data suggests that combination of low dose urokinase with a neuroprotective agent may benefit ischemic stroke treatment by improving neurologic recovery, attenuating infarction size, and reducing the risk of cerebral hemorrhage.

Animals↗
PubMed2000

Acute ethanol administration and transient ischemia: a behavioral and neuropathological study.

A pressing clinical question is how acute ethanol exposure might alter the outcome of a simultaneous transient ischemic attack (TIA), since ethanol is known to dysregulate key intermediary metabolites post-ischemia. Mongolian gerbils were administered ethanol (1 or 4 g/kg, s.c.) 1 hour before induction of transient ischemia, via bilateral carotid occlusions of 5 minutes duration. A control group was administered isotonic saline and rendered ischemic. All animals were maintained normothermic during the ischemic procedure. Subjects underwent behavioral assay of acquisition to the water maze 7 days after recovery from the surgery, and neuropathological examination 1-month after the ischemic brain insult. There were no behavioral or neuropathological between-group differences suggesting that mechanisms other than adverse ethanol-induced perturbations of ischemic processes predominate in mediating epidemiological findings of elevated stroke morbidity with high ethanol consumption.

Animals↗
PubMed2000

Evaluating the efficacy of citicoline in embolic ischemic stroke in rats: neuroprotective effects when used alone or in combination with urokinase.

The combination of thrombolysis with neuroprotection, because of different mechanisms, would be expected to show better results when used after onset of focal ischemia. In this study we report our experience with the neuronal protective effects of citicoline alone and in combination with urokinase in a model of focal ischemia. Both medications were injected 2 h after onset of a focal occlusion of the middle cerebral artery (MCA) in rats. Focal ischemia was produced with embolization of a clot into the origin of the MCA. This produces a large infarction involving the cortex and the basal ganglia. Animals were observed for neuronal deficts at 2 and 24 h after surgery and were sacrificed 72 h after onset of ischemia. Saline-treated animals showed a large infarction involving the cerebral cortex and basal ganglion in most animals (volume 33.1 +/- 9.7%). Animals treated with citicoline alone were divided in two groups. The first group of animals were treated with a single injection (300 mg/kg, ip) of the medication 2 h after the arterial occlusion. The second group was treated with the active medication intermittently (3 x 300 mg/kg, ip) over a 72-h period. There was a significant decrease in the neuronal damage in the cortex in the animals treated with citicoline (single dose, 20.9 +/- 9.7%, P = 0.01; intermittent injection, 18.9 +/- 11.4%, P < 0.008). The last experiment evaluated the usefulness of the combination of citicoline with intraarterial urokinase. The combination showed significantly more protection than with urokinase or citicoline alone (volume 13.6 +/- 9.1%, P < 0.001). We conclude from our experiments that citicoline may offer significant neuronal protection that may be further enhanced with the addition of a thrombolytic agent.

Animals↗
PubMed2000

Neuroprotection by 2-h postischemia administration of two free radical scavengers, alpha-phenyl-n-tert-butyl-nitrone (PBN) and N-tert-butyl-(2-sulfophenyl)-nitrone (S-PBN), in rats subjected to focal embolic cerebral ischemia.

Oxygen free radical generation may have important secondary damaging effects after the onset of cerebral ischemia. Free radical scavengers have been used successfully in attenuating neuronal damage in the reperfusion period in transient forebrain ischemia. There are limited data on effectiveness in models of focal ischemia. Two free radical scavengers, alpha-phenyl-n-tert-butyl-nitrone (PBN) and N-tert-butyl-(2-sulfophenyl)-nitrone (S-PBN), have been shown to reduce oxidative-stress-induced neuronal injury. Whereas PBN has been demonstrated to reduce infarct volume in focal ischemia, neuroprotection has not been evaluated with S-PBN. The present study was designed to evaluate the neuroprotective effect of PBN and S-PBN compared to vehicle in a focal embolic middle cerebral artery (MCA) cerebral ischemia model in rats. Wistar rats were randomly divided into three groups (n = 10 each group). Animals in the control group received vehicle and those in the treatment groups were treated with PBN or S-PBN (both 100 mg/kg/day x 3 days, intraperitoneally) starting 2 h after the introduction of an autologous thrombus into the right-side MCA. The neurological outcome was observed and compared before and after treatment and between groups. The percentage of cerebral infarct volume was estimated from 2,3, 5-triphenyltetrazolium chloride stained coronal slices 72 h after the ischemic insult. Two-hour postischemia administration of PBN or S-PBN significantly improved neurobehavioral scores at 24 h following MCA embolization (both P < 0.01). The percentage of infarct volume for animals receiving vehicle was 32.8 +/- 9.4%. Two-hour delayed administration of PBN and S-PBN achieved a 35.4% reduction in infarct volume in treatment groups when compared with animals receiving vehicle (PBN vs control, 21.2 +/- 10.9% vs 32.8 +/- 9.4%; P < 0.05; S-PBN vs control, 21.2 +/- 13.1%, (P < 0.05). These data indicate that free radical generation may be involved in brain damage in this model and 2-h delayed postischemia treatment with PBN and S-PBN may have neuroprotective effects in focal cerebral ischemia. As S-PBN does not normally cross the blood-brain barrier, the neuroprotection evident in this study may be explained by entry into the brain via damaged vessels.

Animals↗
PubMed2000

Vertebral artery dissection: warning symptoms, clinical features and prognosis in 26 patients.

BACKGROUND AND OBJECTIVES: Internal carotid artery dissection has been extensively studied and well-described. Although there has been a recent increase in the number of reported cases of vertebral artery (VA) dissection, the clinical variety of presentation and the early warning symptoms have not been well-described before. Our objectives in this study include: (1) To determine the early symptoms and warning signs which may help the clinician in the early identification and treatment of patients with VA dissection. (2) To explore the variety of clinical presentation of VA dissection and its relation to prognosis. DESIGN AND SETTING: Retrospective analysis of hospital records in a tertiary academic centre for the period 1989-1999. RESULTS: Twenty-six patients were identified (13 men and 13 women). The mean age was 48. Possible precipitating factors were identified in 14 patients (53%). Sporting activity and chiropractic manipulations were the most common (15% and 11% respectively). Headache and/or neck pain was the prominent feature in 88% of patients and was a warning sign in 53%, preceding onset of stroke by up to 14 days. The most common clinical features included vertigo (57%), unilateral facial paresthesia (46%), cerebellar signs (33%), lateral medullary signs (26%) and visual field defects (15%). Bilateral VA dissection presented in six patients (24%). The most common region of dissection was the C1-C2 level (16 arteries, 51%). Intracranial VA dissection was found in eight arteries (25%). The majority of patients (83%) had favorable outcome. Poor prognosis was associated with (1) bilateral dissection; (2) intracranial VA dissection accompanied by subarachnoid hemorrhage. Only two patients reported stroke recurrence. CONCLUSIONS: Our findings show that VA dissection affects mainly middle age persons and involves both sexes equally. Headache and/or neck pain followed by vertigo or unilateral facial paresthesia is an important warning sign that may precede onset of stroke by several days. Although the majority of patients will have excellent prognosis, this was less likely in patients presenting with subarachnoid hemorrhage or bilateral VA dissection. Recurrence rate was low.

Adult↗
PubMed2000

The role of taurine in neuronal protection following transient global forebrain ischemia.

Osmoregulation and post ischemic glutamate surge suppression (PIGSS) are important mechanisms in the neuroprotective properties of taurine. We studied the role of taurine in PIGSS following transient global forebrain ischemia (TGFI). A group of gerbils received a high dose of continuous intracerebral taurine during the peri-ischemic period. Beta-alanine was given similarly to a negative control group. The control group consisted of animals undergoing only TGFI. On the fourth day following commencement of drug administration, TGFI was induced. Concurrently, half the animals from each group receiving an agent had intracerebral microdialysis. All animals underwent histological assessment at day 7. The microdialysis and histological data was analyzed. Our results showed that taurine treatment did not cause PIGSS. The histological difference between the three groups was statistically insignificant. We conclude that intracerebral taurine in the dosage administered during peri-ischemic period, does not result in PIGSS or histologically evident neuroprotection.

Animals↗
PubMed2000

Design of the blockade of the glycoprotein IIb/IIIa receptor to avoid vascular occlusion (BRAVO) trial.

BACKGROUND: Platelets play a key role in the pathogenesis of atherosclerosis, thrombosis, and acute coronary and cerebrovascular syndromes. Inhibition of platelet function by acetylsalicylic acid (aspirin) has been shown to reduce the incidence atherothrombotic events in patients with coronary, cerebrovascular, or peripheral vascular disease. Thienopyridine agents, however, including ticlopidine and clopidogrel, inhibit the adenosine diphosphate receptor and have modestly superior effects compared with aspirin on reduction of death, myocardial infarction, and stroke among a broad group of patients with vascular disease. More effective antithrombotic agents are still required to treat patients at high risk for recurrent vascular events. METHODS: Lotrafiban, a selective, nonpeptide antagonist of the human platelet fibrinogen receptor (glycoprotein [GP] IIb/IIIa [alphaIIb/beta3 integrin]), blocks the binding of fibrinogen to the GP IIb/IIIa receptor, which is the final common pathway of platelet aggregation. Lotrafiban at doses of up to 50 mg twice daily was well-tolerated in a 12-week, double-blind, placebo-controlled, dose-ranging study in patients with recent myocardial infarction, unstable angina, transient ischemic attack, or stroke when added to aspirin therapy. On the basis of these results, a dosing regimen was selected for the phase III Blockage of the Glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion (BRAVO) trial based on pharmacodynamics and drug tolerability. In the pivotal BRAVO study, lotrafiban therapy is being evaluated in patients who have had a recent myocardial infarction, unstable angina, transient ischemic attack, or ischemic stroke, or who present at any time after a diagnosis of peripheral vascular disease combined with either cardiovascular or cerebrovascular disease. RESULTS: The efficacy evaluation will be based on a composite end point of clinical events (death by any cause, myocardial infarction, stroke, recurrent ischemia requiring hospitalization, or urgent ischemia-driven revascularization). The target enrollment is 9200 patients worldwide. Approximately 700 centers will participate and will be distributed within 30 countries across North America, Europe, Australia, and Asia.

Administration, Oral↗
PubMed2000

Hyperglycemia enhances extracellular glutamate accumulation in rats subjected to forebrain ischemia.

BACKGROUND AND PURPOSE: An increase in serum glucose at the time of acute ischemia has been shown to adversely affect prognosis. The mechanisms for the hyperglycemia-exacerbated damage are not fully understood. The objective of this study was to determine whether hyperglycemia leads to enhanced accumulation of extracellular concentrations of excitatory amino acids and whether such increases correlate with the histopathological outcome. METHODS: Rats fasted overnight were infused with either glucose or saline 45 minutes before the induction of 15 minutes of forebrain ischemia. Extracellular glutamate, glutamine, glycine, taurine, alanine, and serine concentrations were measured before, during, and after ischemia in both the hippocampus and the neocortex in both control and hyperglycemic animals. The histopathological outcome was evaluated by light microscopy. RESULTS: There was a significant increase in extracellular glutamate levels in the hippocampus and cerebral cortex in normoglycemic ischemic animals. The increase in glutamate levels in the cerebral cortex, but not in the hippocampus, was significantly higher in hyperglycemic animals than in controls. Correspondingly, exaggerated neuronal damage was observed in neocortical regions in hyperglycemic animals. CONCLUSIONS: The present results demonstrate that, at least in the neocortex, preischemic hyperglycemia enhances the accumulation of extracellular glutamate during ischemia, providing a tentative explanation for why neuronal damage is exaggerated.

Alanine↗
PubMed2000

Usefulness of postischemic thrombolysis with or without neuroprotection in a focal embolic model of cerebral ischemia.

OBJECT: Recent studies have shown that the use of thrombolysis in the setting of acute stroke is associated with an increased risk of cerebral hemorrhage. The time of onset of symptoms to initiation of medication and the dose levels of the thrombolytic agents are important determinants for the risk of cerebral hemorrhage. The authors evaluated the time course of thrombolysis-related hemorrhages in experimental settings and tested whether the addition of neuroprotective medication augments the efficacy of thrombolysis and reduces the incidence of hemorrhages. METHODS: Male Wistar rats were subjected to right middle cerebral artery embolization with an autologous thrombus and were then randomly assigned to one of the following groups: Group 1, saline-treated (2 hours after ischemic insult) animals as controls; Groups 2 to 4, high-dose urokinase (5,000 U/kg) at 2, 3, and 6 hours after the insult; Group 5, low-dose urokinase (2,500 U/kg) at 2 hours after the insult; Group 6, 20 mg/kg topiramate (TPM) at 2 hours after the insult; Group 7, a combination of 20 mg/kg TPM at 2 hours and low-dose urokinase (2,500 U/kg) at 6 hours after the insult; and Group 8, 20 mg/kg TPM (20 mg/kg) at 2 hours and high-dose urokinase (5,000 U/kg) at 2 hours after the insult. Neurological behavior and the infarct volume in the brain were assessed following cerebral embolism and the various treatments. All animals in the single therapy and low-dose combination groups survived surgery. Three of eight animals treated with high-dose urokinase alone at 6 hours and three of six animals in the combined high-dose urokinase and TPM group developed fatal intracerebral hemorrhages. There was a significantly better neurological outcome at 24 hours in the animals treated with either medication compared with controls. The volume of the infarct in the saline-treated group was 54.2 +/- 9%. The use of TPM at 2 hours led to a decrease in the infarct to 20.1 +/- 11.2% (p < 0.01). Treatment with urokinase at 6 hours after the occlusion showed a trend toward protection; the infarct volume was 31.9 +/- 14.1% (p < 0.05). The addition of TPM to low- or high-dose urokinase achieved better neuroprotection (8.2 +/- 6% and 11.9 +/- 10.7%, respectively; both p < 0.01). CONCLUSIONS: In this study the authors show that the volume of the infarct can be significantly decreased with 2 to 6-hour delayed intraarterial thrombolysis with urokinase and that the efficacy of thrombolysis may be enhanced by combining neuroprotective agents like TPM. It is also shown that low-dose combination therapy may decrease the likelihood of cerebral hemorrhage.

Acute Disease↗
PubMed1999

Hypothermia ameliorates ischemic brain damage and suppresses the release of extracellular amino acids in both normo- and hyperglycemic subjects.

It has previously been shown that hypothermia markedly reduces cellular release of the excitatory amino acid glutamate and ameliorates ischemic damage. Based on extensive data showing that preischemic hyperglycemia exaggerates brain damage due to transient forebrain ischemia we posed the question whether glutamate release during ischemia in hyperglycemic rats is attenuated or prevented by induced hypothermia, and if such attenuation/prevention correlates with amelioration of the characteristic brain damage observed in hyperglycemic subjects. The experiments were performed in rats subjected to a 15-min period of forebrain ischemia, plasma glucose concentration being maintained at approximately 5 mM (control) or approximately 20 mM (hyperglycemia) prior to ischemia. Extracellular amino acid concentrations were measured by HPLC techniques on microdialysis samples which were collected from left dorsal hippocampus and right neocortex, and tissue damage was assessed by histopathology. Hypothermia (30 degrees C), which was induced 45 min prior to ischemia, reduced the neuronal damage not only in the ischemia-vulnerable regions but also in the normally ischemia-resistant areas that are recruited in the damage process in hyperglycemic subjects. The extracellular glutamate concentration was markedly increased in response to the ischemic insult in normothermic-normoglycemic animals. The concentration of glutamate was further increased in normothermic-hyperglycemic animals. Hypothermia inhibited the rise in glutamate concentrations, as well as in the concentrations of other excitatory and inhibitory amino acids. It is discussed whether hypothermia reduces the hyperglycemia-mediated damage by inhibiting extracellular glutamate release during an ischemic transient.

Animals↗
PubMed1999

Genetic markers on HIV-1 gp120 C2-V3 region associated with the expression or absence of cognitive motor complex in HIV/AIDS.

In the CNS, HIV-1 causes cognitive motor complex (CMC) in about 30-40% of patients. To explain CMC physiopathology: disequilibrium of cytokine networks, calcium influx, free radicals and toxic effects by HIV-1 have been evoked. Neurotropic mutants have not been unambiguously proven nor 'variants' of HIV-1 with biological properties that could cause CMC. By computerized analysis of gp120 C2-V3 subtype B sequences from retroviral databases, and applying stringent criteria, we found: (i) mutations specific for CMC; (ii) mutations associated with the absence of CMC (N-CMC); (iii) mutations with specificity for the geographical region of origin, and finally (iv) shared mutations representing 'hot spots.' We suggest that the capability to cause or not to cause CMC may be present in the virus prior to infection. In the future, these markers could be used to guide treatments with novel neuroprotective regimes.

AIDS Dementia Complex↗
PubMed1998

Quantification of infarct size on focal cerebral ischemia model of rats using a simple and economical method.

Quantification of infarct size is a very useful index to assess models of focal cerebral ischemia and effects of new therapies. Currently-used image analysis systems to carry out this task usually involve dedicated and expensive equipment. We present a low-cost and simple method to perform the image acquisition and analysis. Twelve Wistar rats were subject to focal cerebral ischemia and scarified 24 h after the insult. 2,3,5-triphenyl tetrazolium chloride (TTC) stain was used as a conventional method to differentiate ischemic damage from healthy brain tissue. Digital images were captured from the stained coronal sections using a flatbed color scanner and analyzed with a commercial image processing software. To evaluate the accuracy and reproducibility of this method, the data obtained with the current procedure was correlated with those from a dedicated standard image analysis system and intra-observor correlation coefficient was estimated. Also the sensitivity of this method in quantification of infarct volume was tested in two different experimental settings. There was close correlation in the outcome of infarct size measurement between the current method and the standard system (r = 0.93, p < 0.001). A high agreement of measurement of the percentage of infarct volume between two different examiners with the same source of samples (r = 0.98, p < 0.001). We demonstrated that this method was sensitive in detection of difference of infarct sizes when placebo-treated animals (n = 6) were compared to the group treated with a neuroprotective agent (n = 6). Our data demonstrated that ischemic lesion of focal cerebral ischemia in rat can be accurately and reproducibly quantified using this method. The low-cost and simplicity of this method may facilitate the application in determination of ischemic damage.

Animals↗
PubMed1998

Neuroprotection by delayed administration of topiramate in a rat model of middle cerebral artery embolization.

Because topiramate (TPM) suppresses voltage-sensitive Na+ channels and non-N-methyl-D-aspartate (NMDA) receptors and enhances gamma-aminobutyric acid (GABA)-mediated inhibition, we tested whether it would protect against cerebral ischemia. The right middle cerebral artery (MCA) was embolized by an intra-arterial injection of autogenous thrombus. Two hours after thrombus injection, animals received intra-peritoneal injections (i.p.) of normal saline as control (n=6) or alternatively, a low- (20 mg/kg, i.p., n=6) or high-dose (40 mg/kg, i.p., n=6) of TPM. Neurological deficit was scored at 2 h and 24 h following the ischemic insult. The animals were sacrificed 24 h after ischemia and the coronal brain sections were stained with 2% 2,3,5-triphenyltetrazolium chloride (TTC) for determination of the percentage of infarct volume. Administration of TPM significantly improved the 24-h neurological deficit scores (low dose, 1.75+/-0.5; high dose, 1.17+/-0.41; p<0.05 for both doses). A reduction in the percentage of infarct volume (low dose, 22.9+/-8.9%, p=0.002; high dose 7.6+/-3.4%, p<0.001) was seen when compared to the controls (infarct size, 54.2+/-9.0%; neurobehavior score, 2. 67+/-0.52). Treatment with TPM at the higher dose induced more neuroprotection than that at the lower dose (p<0.05). Thus, treatment with TPM resulted in a dose- and use-dependent neuroprotective effect, when used 2 h after MCA embolization in a rat model of focal ischemia.

Animals↗