Biomedical subjects

A Shuaib

Publications and source records attributed to A Shuaib.

At least 19 recordsLinked to original sources

PubMed1997

Effects of clomethiazole on radial-arm maze performance following global forebrain ischemia in gerbils.

The functional and neuroanatomical protective effects of clomethiazole (CMZ) were examined in an animal model of global forebrain ischemia. Gerbils underwent sham-surgery or were rendered ischemic by the application of aneurysm clips to both carotid arteries for 6 min. Three treatment groups received CMZ (50 mg/kg, 100 mg/kg, or 150 mg/kg) 30 min before ischemia, and one group was given 150 mg/kg of CMZ 30 min after ischemia. Following recovery, the gerbils were tested in a radial-arm maze to assess memory functions. Histological evaluation was assessed blindly using a percentile scoring system. The results indicate that pre-ischemic treatment with 100 mg/kg and 150 mg/kg of CMZ reduced brain damage and working memory errors significantly. Treatment dosage of 150 mg/kg of CMZ was the most effective in preventing neuronal damage in the hippocampus and eliminating the working memory deficit typically induced by ischemia.

Animals↗

PubMed1997

Inhibitory mechanisms in cerebral ischemia: a brief review.

Cessation of cerebral blood flow results in severe damage to neurons and other brain structures. This is secondary to a combination of energy loss, excessive excitation promoting intracellular Ca2+ buildup, relative lack of inhibitory responses, generation of oxygen free radicals, especially during the reperfusion period and several other destructive cascades. Therapies aimed at decreasing the ill effects of glutamate are either not effective or have serious side-effects. Ca2+ entry blockers are generally not effective in cerebral ischemia, and data with protective effects of oxygen free radical scavengers in the post-ischemic period have shown conflicting results. There is recent interest with the use of agents that increase cerebral inhibitory responses after an ischemic insult. Such agents are effective when used before, during or up to 4 h after the ischemic insult. Many such medications have few side-effects and are in clinical use for other indications. This review will summarize inhibitory mechanisms that may be important in cerebral ischemia, and provide experimental evidence for their potential efficacy.

Animals↗

PubMed1997

EC-IC bypass improves chronic ischemia in a patient with moyamoya disease secondary to sickle cell disease: an in vivo microdialysis study.

Patients with sickle cell disease may develop intracranial vascular disease, with the occlusion or obstruction of the large or small arteries, which may lead to the secondary development of moyamoya disease. In this report, we describe the neurochemical changes in the brain before, during, and after an extracranial-intracranial bypass procedure on a patient with sickle cell disease and a moyamoya disease like pattern on angiography. We used the in vivo microdialysis technique to measure the on-line pH, lactate and amino acid concentrations in the extracellular fluid. There were relatively high resting glutamate levels and a lower-than-normal pH in the extracellular fluid prior to the bypass, associated with chronic ischemia. During the bypass there was a short-lived increase in the glutamate levels. After revascularization, there was a rapid decrease in the glutamate levels and an increase in the pH value. The patient's preoperative neurological deficit improved post-operatively, corresponding to the biochemical changes towards normal values. These changes after revascularization suggest that chronic biochemical abnormalities due to brain ischemia may improve after cerebral revascularization.

Adult↗

PubMed1997

Amplification of inhibitory mechanisms in cerebral ischemia: an alternative approach to neuronal protection.

The central nervous system consumes 20% of the cardiac output for normal function. The neurons are very sensitive to the effects of ischemia. Cessation of cerebral blood flow results in severe damage to neurons and other brain structures. This is secondary to a combination of energy loss, excessive excitation promoting intracellular calcium (Ca2+) buildup, relative lack of inhibitory responses, generation of oxygen free radicals (especially during the reperfusion period) and several other destructive cascades. Medications that antagonize the effects of glutamate at post-synaptic receptors are either ineffective or have serious side-effects. Ca2+ entry blockers have shown disappointing results in clinical trials in patients with acute cerebral infarction. Data with protective effects of oxygen free radical scavengers in the post-ischemic period have shown conflicting results. There is recent interest with the use of agents that increase cerebral inhibitory responses after an ischemic insult. Such agents are effective when used before, during or up to 4 hours after the ischemic insult. Many such medications have few side-effects and are in clinical use for other indications. This review will summarize inhibitory mechanisms that may be important in cerebral ischemia, and provide experimental evidence for their potential efficacy.

Adenosine↗

PubMed1997

Comparative study of 18 gauge and 20 gauge intravenous catheters during transcranial Doppler ultrasonography with saline solution contrast.

A formal technical protocol has not been established for transcranial Doppler ultrasonography in the detection of venous to arterial shunts; techniques have been adapted from contrast echocardiography. We evaluated the effect of different diameter indwelling intravenous catheters on the detection of right-to-left shunts by transcranial Doppler ultrasonography. Fifteen patients underwent transcranial Doppler sonographic evaluation with saline solution contrast using both 18 gauge and 20 gauge indwelling intravenous catheters. The larger bore intravenous catheter delivered a greater number of signals in a shorter time to the insonated middle cerebral artery. We recommend that a standardized method for transcranial Doppler sonographic contrast studies include an 18 gauge intravenous catheter.

Adult↗

PubMed1996

Neuroprotective effects of hypothermia and U-78517F in cerebral ischemia are due to reducing oxygen-based free radicals: an electron paramagnetic resonance study with gerbils.

Free radicals are implicated as causative agents in various forms of tissue destruction. Considerable circumstantial evidence suggests that oxygen-based free radicals generated as blood flow returns to formerly ischemic brain areas are mainly responsible for the neurodegeneration that follows periods of cerebral ischemia. In general, oxygen-based free radicals are highly reactive and exist for only a brief period of time. This makes the direct measurement of many of these free radicals rather difficult. Much of the current knowledge of free radicals in cerebral ischemia is based on observations of chemical changes brought about by the free radicals rather than on direct observations of the free radicals themselves. Low temperature electron paramagnetic resonance spectroscopy is one method that allows the direct study of free radicals. Compared to samples from sham-operated controls, samples of hippocampus taken from gerbils exposed to 15 min of forebrain ischemia followed by 15 min of reperfusion, frozen in liquid nitrogen less than 20 sec after sacrifice, and scanned by low temperature (100 K) electron paramagnetic resonance, show a significant increase in oxygen-based free radicals and a decrease in carbon-based ubiquinone-like free radicals. The ischemia-induced increase in oxygen-based free radicals is prevented by the intraperitoneal injection of the antioxidant drug U-78517F at the start of reperfusion and by hypothermia. However, neither intervention alters the ischemia-induced reduction in the ubiquinone-like free radicals. This suggests that the neuroprotective actions of hypothermia and U-78517F include a direct reduction in the oxygen-based free radical burden of the post-ischemic tissue.

Animals↗

PubMed1996

Neuroprotection with felbamate: a 7- and 28-day study in transient forebrain ischemia in gerbils.

The use of glutamate antagonists and GABA agonists may protect neurons from the effects of transient ischemia. Felbamate is a new antiepileptic drug with glutamate antagonist and GABA agonist properties. We tested the efficacy of felbamate in a gerbil model of transient forebrain ischemia. Damage assessment was done with silver staining at 7 and 28 days after 5 min of bilateral carotid occlusion. Cerebral cortex, hippocampus (CA1 and CA4), thalamus and striatum were evaluated on a 4-point scoring system. The animals sacrificed at 28 days were also tested in a water-maze task to assess recovery of function. The initial dose of felbamate (300 mg/kg) was given 30 min before the ischemic insult in one set of animals and 30 min after the insult in another set of animals. There were 8 animals tested per group (total: 48 animals). There was significant neuronal protection with the use of felbamate, both before and after ischemia in all regions of the brain. Protection was seen in animals sacrificed at 7 and 28 days. Protection was moderate when felbamate was used before ischemia. It was highly significant when felbamate was given 30 min after the insult. Behavioral studies however did not show any difference in the felbamate treated animals versus the saline treated controls. The structural protection with felbamate was very significant when used in the post-ischemic period. This window for protection merits further evaluation in relation to the clinical setting of stroke.

Animals↗

PubMed1996

The effect of age on susceptibility to brain damage in a model of global hemispheric hypoxia-ischemia.

Stroke occurs in all age groups, ranging from the newborn to the elderly. The immature brain is generally believed to be more resistant to the damaging effects of cerebrovascular compromise compared to the more mature brain. However, recent experiments suggest that the correlation between brain damage and age is not linear. To determine the effects of age and development on hypoxic-ischemic brain damage, we developed a model whereby rats of increasing age received identical cerebrovascular insults, and assessed neuropathologic outcome. Male Wistar rats of 1, 3, 6, and 9 weeks and 6 months underwent unilateral common carotid artery ligation and exposure to 12% oxygen for 35 min. Animals were all spontaneously breathing under light halothane anesthesia (0.5%). Core temperatures were maintained at 37 degrees C. Blood pressures were monitored via indwelling carotid artery catheters on the side ipsilateral to the carotid artery ligation. Cerebral blood flow was assessed in separate groups utilizing Laser Doppler flowmetry. Physiologic monitoring revealed that under these experimental conditions, mean arterial blood pressure and cerebral blood flow decreased to the same extent in each of the age groups, verifying that all animals experienced an identical insult. Neuropathologic assessment at 7 days of recovery showed that brain damage was most severe in the 1 and 3 week old animals followed by those that were 6 months. The 6 and 9 week old groups had significantly less injury than the other 3 age groups. Hippocampal damage was most severe in the 3 week and 6 month old rats compared to all other age groups. Our findings contrast previously held beliefs regarding the enhanced tolerance of the immature brain to hypoxic-ischemic damage and demonstrates that, in a physiologically controlled in vivo model of hemispheric global ischemia, (1) the immature brain is, in fact, less resistant to hypoxic-ischemic brain damage than its adult counterpart, (2) the brain damaging effects of hypoxic-ischemia are age dependent, but do not increase linearly with advancing age and development, and (3) the intermediate age groups are more tolerant to hypoxic-ischemic brain injury than either very young or more mature ages.

Acid-Base Equilibrium↗

PubMed1996

Glucose-induced decrease in glutamate levels in ischemic human brain by in-vivo microdialysis.

Glutamate is one of the principal neurotoxins in the pathogenesis of ischemic neuronal injury. Elevated glutamate levels in ischemia have been well documented in many animal stroke models. Recent work in humans also shows a similar trend. We have used our acute focal ischemic model of the human brain to study the response of glutamate levels by in vivo microdialysis during ischemia using two different perfusates. The addition of 30 mM of glucose to the perfusate attenuated the percentages of dialysate glutamate levels from 4.27 +/- 1.7 to 1.34 +/- 0.47 (P < 0.001) during partial ischemia and from 21.42 +/- 6.05 to 7.25 +/- 1.43 (P < 0.05) with total ischemia. The pre-ischemic values of glutamate were similar with the two perfusates. These results indicate that the ischemia-induced rise in glutamate is attenuated by exogenous glucose delivery in the human stroke model.

Amino Acids↗

PubMed1996

The neuroprotective effects of gamma-vinyl GABA in transient global ischemia: a morphological study with early and delayed evaluations.

Enhancing inhibitory mechanisms has been shown to improve neuronal survival after transient focal or global ischemia. In most studies, histological evaluations have been confined to the CA1 region of the hippocampus up to 7 days after an ischemic insult. We have previously shown that continuous intra-ventricular infusion of gamma-vinyl GABA (GVG) results in significant protection after cerebral ischemia. This present study was designed to assess histological and behavioral function at 7 and 28 days after a single 5 min ischemic episode in gerbils. One set of animals received the medication 30 min before the insult and the other set at 1 h after the insult. Evaluation at 7 days showed significant protection in most regions of the brain in both the pre- and post-ischemic treated animals in comparison to the controls. Delayed evaluation at 28 days showed significant protection only in the pre-ischemic treated animals. Behavioral testing with Morris water maze showed no differences in either pre- or post-ischemic treated animals when compared to saline-treated ischemic controls. Our study clearly demonstrates the usefulness of delayed evaluation in the assessment of 'true' neuronal protection. Pre-ischemic treated animals showed persistent and true neuronal protection, in contrast to a temporary protection as seen at 7 days in the post-ischemic treated animals. The lack of behavioral improvement in the pre- and post-ischemic treated animals suggests that morphological protection alone cannot be considered as the sole criterion for successful outcome.

4-Aminobutyrate Transaminase↗

PubMed1996

In-vivo microdialysis study of extracellular glutamate response to temperature variance in subarachnoid hemorrhage.

Neurochemical changes may precede the development of clinical signs in neurological disease. Early identification of such changes may offer an opportunity to avoid or treat complications. Under experimental conditions, extracellular levels of glutamate and other amino acids can be monitored by in-vivo microdialysis in cerebral ischemia, head trauma and epilepsy. Data on the release of glutamate under ischemic conditions in humans are limited. There is no published data on the effects of temperature variation or other manipulations on the extracellular glutamate levels in humans. We report for the first time, the effects of changes in temperature on the extracellular cerebral glutamate levels as measured by in-vivo microdialysis, the dialysate being collected before, during and after cooling in four patients with subarachnoid hemorrhage. Three of the patients had in-vivo microdialysis carried out postoperatively. One patient underwent microdialysis three days prior to the surgical clipping of the aneurysm. In all patients, mild head cooling resulted in a significant decrease in extracellular glutamate levels. The effect of cooling was most apparent when the extracellular glutamate concentrations were high. In two patients, the extracellular glutamate levels increased sharply with fever but returned to normal once the temperature normalized. In vivo microdialysis can be used to measure extracellular glutamate and other neurotransmitters with minimal discomfort in awake humans. This technique offers a unique opportunity to monitor the neurochemistry in critically ill patients and it may aid in developing therapeutic intervention strategies to minimize undesired chemical responses.

Cold Temperature↗

PubMed1996

Evaluation of monoaminergic neurotransmitters in the acute focal ischemic human brain model by intracerebral in vivo microdialysis.

The release of neurotransmitters principally glutamate during cerebral ischemia has been extensively studied. It is well recognized that ischemia induced release of glutamate plays a key role in "excitotoxic" neuronal death. The role of monoaminergic neurotransmitters is however unclear. The purpose of this study was to evaluate the extracellular norepinephrine, 3,4-dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindoleacetic acid (5-HIAA) and serotonin (5-HT) under varied degrees of ischemia in the acute focal ischemic model of the human brain by in-vivo microdialysis. The ischemic response of these amines was correlated with the glutamate levels. Our study concludes that these amines and metabolites can be detected in the human "stroke" model. No marked fluctuations were noted in the levels of norepinephrine and DOPAC. However, significant changes to partial and total ischemia were noted in the extracellular levels of 5-HIAA and 5-HT. These compounds showed a dramatic increase with the onset of ischemia with higher detectable levels in the partial ischemic state in comparison to the total ischemic dialysate levels. The exact role played by the differential increase in the levels of 5-HT to the other catecholamines in the pathogenesis of ischemic neuronal damage remains unclear and warrants further study.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1996

Transcranial Doppler ultrasonography in the detection of venous to arterial shunting in acute stroke and transient ischaemic attacks.

OBJECTIVES: To prospectively evaluate the prevalence of venous to arterial shunting in patients with acute stroke and transient ischaemic attacks (TIAs) using transcranial Doppler ultrasonography (TCD) with saline contrast. METHODS: A consecutive series of patients with stroke or TIA underwent contrast TCD. Patients were subsequently divided into groups according to causative factors for stroke or TIA. The prevalence of right to left shunt was assessed within these groups. RESULTS: A total of 210 patients underwent contrast TCD. A right to left shunt was detected in 28.6% of patients (60 of 210). Among the patients with cryptogenic stroke or TIA, 37.1% (43 of 116) had a positive contrast TCD whereas only 18% (17 of 94) with another identifiable cause had a positive test (P = 0.0024). When age was used to further classify those patients with cryptogenic stroke, TCD was positive in 59.3% patients (16 of 27) of < or = 50 years of age versus 30.3% of patients (27 of 89) > 50 years of age (P = 0.0058). CONCLUSIONS: There was a significantly higher prevalence of venous to arterial shunting in patients with stroke or TIA of undetermined cause than in stroke patients with identifiable aetiologies, as detected by contrast TCD. The prevalence of a venous to arterial shunt was significantly higher in the younger group with cryptogenic stroke. Saline contrast TCD is a relatively non-invasive bedside procedure useful in the detection of venous to arterial shunting.

Acute Disease↗

PubMed1995

Neuroprotective effects of lamotrigine in global ischemia in gerbils. A histological, in vivo microdialysis and behavioral study.

A sudden surge in the release of glutamate is currently believed to be an important initiating step in neuronal damage due to an ischemic insult. In this experiment, we tested the efficacy of neuroprotection with lamotrigine, a novel antiepileptic drug that blocks voltage gated sodium channels and inhibits the ischemia-induced release of glutamate in the gerbil forebrain model of cerebral ischemia. The medication was administered 30 min before and 30 min after the insult in two groups of animals. Histological assessment of neuronal damage was evaluated at 7 and 28 days after the ischemic insult. Animals evaluated at 28 days also underwent behavioral testing. Microdialysis was used in the same model to study the response of ischemia-induced glutamate in saline treated controls versus animals treated with lamotrigine 20 min before the insult. There was highly significant neuronal protection in animals who were treated with lamotrigine either before or after the insult. Protection was seen both at 7 and 28 days after the insult. Behavioral testing also showed significantly better recovery in both sets of animals in comparison to the saline-treated group. Microdialysis confirmed a significant attenuation of the ischemia-induced glutamate surge when compared to the saline-treated animals. Our morphological, behavioral and microdialysis experiments show that lamotrigine offers significant neuroprotection from the effects of transient forebrain ischemia in gerbils. Neuroprotection with post-ischemic therapy probably depends on preserving the capacity of the sodium/calcium exchanger to reduce intracellular calcium concentrations or persistent 'toxicity' of glutamate in the reperfusion period on the already 'primed' injured neurons. These concepts need further study.

Animals↗

PubMed1995

Clomethiazole protects the brain in transient forebrain ischemia when used up to 4 h after the insult.

Brief periods of forebrain ischemia result in consistent damage in the hippocampus in gerbils. This damage can be attenuated by free radical scavengers, glutamate antagonists and GABA agonists. Most of the work with cerebral protection has been done with agents infused prior to the insult. In this experiment we tested clomethiazole, a GABA agonist, as a neuroprotective agent 1 and 4 h after a 5 min ischemic insult (bilateral carotid occlusion) in gerbils. Damage was assessed using silver staining techniques at 7 days after the insult. There were 10 animals in each group. Clomethiazole was given subcutaneously at a dose of 100 mg/kg. Compared to controls, there was significant protection in the CA1 (P < 0.01) and CA4 (P < 0.01) regions of the hippocampus at 1 and 4 h after the ischemic insult. GABAergic agents may play an important role in neuronal protection when used after ischemic insults.

Animals↗

PubMed1995

Post-ischemic therapy with CGS-19755 (alone or in combination with hypothermia) in gerbils.

Hypothermia or a glutamate receptor antagonist may offer protection when used before or within seconds of an ischemic insult. In this experiment, we tested the efficacy of hypothermia (34 degrees C) versus CGS-19755 (a potent competitive N-methyl-D-aspartate (NMDA) receptor blocker) and their combination which was administered 0.5 h after a 5-min forebrain ischemic insult in gerbils. Morphological assessments were done in Group A at the end of 7 days while Group B was evaluated at 29 days. Each group had four sets of animals: saline treated controls; hypothermia treated; CGS-19755 treated; and a combination of CGS-19755 + hypothermia treated animals. Group A showed significant 'protection', i.e. minimal neuronal damage in the animals treated with hypothermia alone. Protection was evident in the cerebral cortex (P < 0.001), hippocampus CA1 (P < 0.01), and in the striatum (P < 0.05). There was no evidence of neuronal protection in the animals that had received either CGS-19755 alone or a combination of hypothermia and CGS-19755. In Group B (29 day assessment) the neuroprotective effects were not evident in any of the animals when compared to the controls. Behavioral testing with Morris water-maze testing showed no significant differences between the control and any of the treated animals. Our data suggests that 'post-ischemic' therapy with hypothermia may delay the effects of ischemia but does not offer significant long-term neuronal protection. Protection seen at 7 days is not evident at 29 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

The effect of post-ischemic hypothermia following repetitive cerebral ischemia in gerbils.

Repetitive ischemia may result in more severe damage than a single similar duration insult. Inter-ischemic hypothermia significantly decreases this damage. It is unclear if protection would be evident if cooling was delayed until after the repeated insults. In this study, we evaluated the effects of 3 h of mild cooling (34-35 degrees C) beginning immediately after the third insult of ischemia, 0.5 h after the third insult and 1 h after the third insult in a gerbil model of repetitive ischemia. Neuronal damage was assessed in the cerebral cortex (CTX), hippocampus (CA1, CA4), striatum (STR), thalamus (THL), medial geniculate nucleus (MGN), and the substantia nigra reticulata (SNr). A '4-point' damage scale was used and evaluation was done in a blinded way. Group comparisons were done using the Mann-Whitney U-test for significance between the control and hypothermic groups. Immediate hypothermia after the third ischemic insult produced a significant protection in the CTX (P < 0.05), hippocampus (CA1 and CA4, P < 0.01), STR (P < 0.001), SNr (P < 0.01), MGN (P < 0.01) and THL (P < 0.01). Cooling at 0.5 and 1 h after the third insult produced no protection when compared to ischemic controls. The window of opportunity with hypothermia is narrow in repetitive ischemia. To be effective, therapy must be initiated as soon as possible after ischemic insults.

Animals↗

PubMed1995

Baclofen is cytoprotective to cerebral ischemia in gerbils.

The release of the neurotransmitter, glutamate, and the activation of receptor operated calcium channels, may increase the degree of damage in ischemic brain tissue. Inhibition of excitatory neurotransmitters should therefore result in cytoprotection of ischemic brain tissue. In this study we evaluated the effect of baclofen, an inhibitor of presynaptic glutamate release, on ischemic gerbil cortex, hippocampus (CA 1 and CA4), striatum and thalamus. Histological evaluation was done in a blind manner in 4 groups (total 36 animals): a control group (9 animals) and three groups (27 animals) with varying doses of baclofen. For cerebral ischemia, we used single episode of five minutes of arterial occlusion of the carotid arteries. Baclofen in doses of 0, 25, 50, and 100 mg/kg were given to different groups five minutes prior to ischemic insult. This was followed by intraperitoneal injections given 24 and 48 hours after the initial insult. Statistically significant histological cytoprotection was demonstrated. Doses of 25 mg/kg appeared to demonstrate significant protection of the cortex (p = 0.0002), the CA1 and CA4 regions of the hippocampus (p = 0.0004 and 0.0001) respectively. At a dose of 50 mg/kg, significant cytoprotection was demonstrated at the hippocampus (CA1 and CA4 regions), in particular at the CA4 region (p = 0.0029). The 100 mg/kg dose appeared to have most significant protection at the CA1 and CA4 regions of the hippocampus (both p = 0.0001), striatum (p = 0.0011), and the thalamus (p = 0.0008). All statistical comparisons were done using non-parametric tests (Mann-Whitney U test). Our study demonstrates that baclofen is cytoprotective to ischemic neuronal cells, especially in the hippocampus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗