Biomedical subjects

Ashfaq Shuaib

Publications and source records attributed to Ashfaq Shuaib.

52 records · Page 3Linked to original sources

PubMed2003

Antiischemic effects of topiramate in a transient global forebrain ischemia model: a neurochemical, histological, and behavioral evaluation.

The mechanisms of action of the anticonvulsant topiramate (TPM) are indicative of a potential benefit during cerebral ischemia. TPM was studied in a transient global forebrain ischemia (TGFI) model in gerbils in which 40 mg/kg was administered before or after TGFI. Control groups were administered 0.9% normal saline similarly. The evaluation consisted of neurochemical, histological, and functional analyses. The data obtained indicates that unlike the focal cerebral ischemia model, TPM is not neuroprotective in TGFI. The difference in effect, which may be due to the difference in species or the type of ischemia, points to the need for caution when extrapolating animal data from this drug to humans.

Animals↗

PubMed2003

Applicability, validity, and reliability of the Piper Fatigue Scale in postpolio patients.

OBJECTIVE: To identify a scale that is potentially applicable for measuring the fatigue in postpolio patients and to evaluate its validity and reliability in this population. DESIGN: Interview survey of 64 individuals with postpolio syndrome and 25 healthy controls of similar age range, with retest in a subset of postpolio patients. The sample was recruited from a postpolio support group, a postpolio clinic, and the general community. Subjects completed the Piper Fatigue Scale, the Beck Depression Inventory, and the Chalder Fatigue Questionnaire during the interview. RESULTS: Face and content validity of the Piper Fatigue Scale was established by a team of experts and by a group of postpolio patients. The postpolio subjects had significantly higher Piper Fatigue Scale scores than the healthy control subjects (P < 0.001), demonstrating extreme groups validity. Convergent validity was shown with a strong positive correlation between Piper Fatigue Scale scores and Chalder Fatigue Questionnaire scores (r = 0.80). Reliability was also demonstrated with the Piper Fatigue Scale's high internal consistency (alpha = 0.98) and strong test-retest agreement (intraclass correlation coefficient = 0.98). CONCLUSIONS: The Piper Fatigue Scale is a valid and reliable tool for measuring postpolio fatigue. This scale may be useful in other studies of postpolio fatigue, including those gauging the effectiveness of various treatments for this fatigue.

Activities of Daily Living↗

PubMed2003

Reduced brain infarct volume and improved neurological outcome by inhibition of the NR2B subunit of NMDA receptors by using CP101,606-27 alone and in combination with rt-PA in a thromboembolic stroke model in rats.

OBJECT: A novel postsynaptic antagonist of N-methyl-D-aspartate (NMDA) receptors, CP-101,606-27 may attenuate the effects of focal ischemia. In current experiments, the authors investigated its neuroprotective effect alone and in combination with recombinant tissue plasminogen activator (rt-PA) in thromboembolic focal cerebral ischemia in rats. METHODS: Forty-eight male Wistar rats underwent embolization of the right middle cerebral artery to produce focal cerebral ischemia. After random division into six groups (eight rats in each group), animals received: vehicle; low-dose (LD) CP-101, 606-27, 14.4 mg/kg; high-dose (HD) CP- 101,606-27, 28.8 mg/kg; rt-PA, 10 mg/kg; low-dose combination (LDC) CP- 101,606-27, 14.4 mg/kg plus rt-PA, 10 mg/kg; or high-dose combination (HDC) CP- 101,606-27, 28.8 mg/kg plus rt-PA, 10 mg/kg) 2 hours after induction of embolic stroke. Animals were killed 48 hours after the onset of focal ischemia. Brain infarction volume, neurobehavioral outcome, poststroke seizure activity, poststroke mortality, and intracranial hemorrhage incidence were observed and evaluated. Compared with vehicle-treated animals (39.4 +/- 8.6%) 2 hours posttreatment with CP-101,606-27 or rt-PA or in combination a significant reduction in the percentage of brain infarct volume was seen (LD CP-101,606-27: 20.8 +/- 14.3%, p < 0.05; HD CP-101,606-27: 10.9 +/- 3.2%, p < 0.001; rt-PA: 21.1 +/- 7.3%, p < 0.05; LDC, 18.6 +/- 11.5%, p < 0.05; and HDC: 15.2 +/- 10.1%, p < 0.05; compared with control: 39.4 +/- 8.6%). Combination of CP-101,606-27 with rt-PA did not show a significantly enhanced neuroprotective effect. Except for the control and LDC treatment groups, neurobehavioral outcome was significantly improved 24 hours after embolic stroke in animals in all other active therapeutic groups receiving CP-101,606-27 or rt-PA or in combination. The authors also observed that treatment with HD CP-101,606-27 decreased poststroke seizure activity. CONCLUSIONS: The data in this study suggested that postischemia treatment with CP-101,606-27 is neuroprotective in the current stroke model; however, the authors also note that although rt-PA may offer modest protection when used alone, combination with CP-101,606-27 did not appear to enhance its effects.

Animals↗

PubMed2002

Failure of delayed and prolonged hypothermia to favorably affect hemorrhagic stroke in rats.

Prolonged hypothermia reduces global and focal cerebral ischemic injury in rodents even when delayed for hours. However, it is not known whether hypothermia can reduce injury following intracerebral hemorrhage (ICH). Accordingly, we studied striatal injury and concomitant motor deficits after 2 days of hypothermia, induced 1 h after creation of an ICH by infusion of bacterial collagenase. Rats were first trained to retrieve food pellets in the Montoya staircase task. They were then implanted with core temperature telemetry probes and later subjected to normothermic ICH or sham operation (vehicle injection). Half self-regulated temperature after surgery; others were cooled to 33 degrees C (24 h) and then 35 degrees C (24 h). Hypothermia did not affect behavioral scores of sham animals (89.8% of baseline in staircase test) or histology. Untreated (normothermic) ICH rats lost 23.1 mm(3) of tissue at a 1-month survival, which significantly impaired food pellet retrieval (66.0% retrieval) with the contralateral limb (tested on days 21-25). Contrary to our hypothesis, hypothermia failed to lessen either the reaching impairment (62.8%) or the lesion (22.2 mm(3)). While other hemorrhagic insults or complications may be improved with hypothermia, our data suggest that it will not salvage tissue that is quickly lost after ICH. We also assessed walking across a horizontal ladder and spontaneous paw usage in a cylinder test at 1-4 weeks after ICH, but neither test was sufficiently sensitive to this mild insult. This indicates that skilled reaching is more severely disrupted than spontaneous paw usage or walking after a striatal hemorrhage.

Animals↗

PubMed2002

A new reproducible focal cerebral ischemia model by introduction of polyvinylsiloxane into the middle cerebral artery: a comparison study.

A reliable focal cerebral ischemia model is essential in evaluating the efficacy and safety of neuroprotective therapy for stroke. We present a focal embolic ischemic model of rat with reproducible and predictable brain infarction by comparing it with two other most commonly used focal cerebral ischemia models. To produce embolic focal cerebral ischemia, 30 male Wistar rats were subjected to injection of 30 microl hydrophilic polyvinylsiloxane (PVS) or an autologous thrombus or intraluminal filament occlusion in the right middle cerebral artery (MCA) (n = 10 in each group). The percent of brain infarct volume at 48 h after ischemia, neurobehavioral score at 2 h before and after ischemia, intracranial hemorrhagic incidence, and premature reperfusion rate at 3 h after ischemia by MCA angiography were assessed respectively and compared between the focal cerebral models. We found that PVS-induced focal cerebral ischemia had more consistent brain infarct size with less dispersion (32.2+/-7.4%, CV = 0.23) than that with an intraluminal filament occlusion (27.6+/-11.4%, CV = 0.41) or an autologous thrombus embolization (27.2+/-11.8%, CV = 0.43). Injection of PVS also caused more severe neurobehavioral deterioration (3.8+/-0.4) than those produced by two other models (filament, 3.1+/-0.9, P = 0.02; thrombotic, 3.5+/-0.5, P = 0.08). Additionally, animals with PVS-induced focal cerebral ischemia suffered less intracranial hemorrhage (PVS, 0/10, filament, 3/10, thrombotic, 3/10), and less premature reperfusion as determined by MCA angiography (PVS, 0/10, filament, 4/10, thrombotic, 3/10). Our data suggests that permanent focal cerebral ischemia with high reproducibility and low mortality can be achieved by introducing PVS into the right MCA.

Animals↗

PubMed2002

Neuroprotective effect of tiagabine in transient forebrain global ischemia: an in vivo microdialysis, behavioral, and histological study.

The neuroprotective effect of tiagabine was investigated in global ischemia in gerbils. Two groups of the animals received 15 mg/kg of tiagabine 30 min before ischemia. In the first group, the temperature was controlled at 37 degrees C from time of injection to 1 h after ischemia. In the second group, the temperature was left uncontrolled to see the hypothermic effect of tiagabine. Microdialysis was performed in CA1 region of hippocampus in half of the animals in each group to assess the levels of glutamate and gamma-amino-butyric acid (GABA). Animal behavior was also tested in 28-day groups in a radial-arm maze. Histology was done 7 and 28 days after ischemia in CA1 region of hippocampus to assess early and delayed effect of drug. A significant suppression of glutamate was noted in both groups (P<0.01). Behavioral results showed that in the temperature-uncontrolled treatment group, animals significantly reduced their working memory errors as compared to the temperature-controlled treatment group. Histology revealed a significant neuroprotection (P<0.001) in the temperature-uncontrolled treatment group. In the temperature-controlled treatment group, however, neuroprotection was insignificant (P>0.05). A third group of animals received the same dose of tiagabine 3 h after ischemia. Temperature was not controlled in this group. The animals were sacrificed after 7 days so no behavior testing was carried out. Histology showed no neuroprotection in this group (P>0.05). These results show that tiagabine offers a significant neuroprotection in global ischemia in gerbils when given 30 min before ischemia but not when given 3 h after ischemia.

Animals↗

PubMed2002

Expression of tumor necrosis factor alpha and its mRNA in the spinal cord following a weight-drop injury.

The effect of traumatic spinal cord injury (SCI) on the expression of tumor necrosis factor (TNFalpha) and its mRNA was examined. Quantitative reverse transcription polymerase chain reaction assay showed TNFalpha mRNA level increased > 20-fold at the lesion site by 1 h after the injury compared to that in uninjured controls. The TNFalpha mRNA level was still significantly higher than in the controls 72 h after the injury. TNFalpha mRNA in the samples collected immediately caudal to the lesion site was also increased. Levels of TNFalpha protein, determined by a cytotoxic bioassay, were also significantly increased at the lesion site. The TNFalpha protein level was maximal 1 and 8 h after the injury and still significantly higher than in the controls 24 h post-injury. The present results demonstrate that TNFalpha is rapidly induced in the spinal cord after the injury, and it may play a significant role in secondary events in SCI.

Animals↗

PubMed2002

Delayed minocycline but not delayed mild hypothermia protects against embolic stroke.

BACKGROUND: Inflammatory reactions occurring in the brain after ischemia may contribute to secondary damage. In the present study, effects of minocycline, an anti-inflammatory agent, alone or in combination with mild hypothermia on focal embolic cerebral ischemia have been examined. METHODS: Focal ischemic injury was induced by embolizing a preformed clot into the middle cerebral artery (MCA). Infarction volume was measured at 48 h after the injury. Mortality was also recorded. RESULTS: Delayed administration of minocycline alone or delayed minocycline plus delayed mild hypothermia reduced the infarction volume significantly. However, delayed mild hypothermia alone was not protective and delayed mild hypothermia in combination with minocycline did not show any additive effect. CONCLUSIONS: These results suggest that minocycline is beneficial in focal ischemic brain injury, and the lack of the enhanced neuroprotection may be due to the brief exposure to hypothermia.

Animals↗

PubMed2002

Trimetazidine as a potential neuroprotectant in transient global ischemia in gerbils: a behavioral and histological study.

The effect of Trimetazidine (TMZ) as a potential neuroprotectant against stroke was studied in the gerbil model of transient forebrain global ischemia. Animals were subjected to a 5-min period of ischemia and assessed 4 and 21 days later. Gerbils were divided into two groups: in group one, gerbils were treated with TMZ at a dose of 25 mg/kg given by intraperitoneal injection prior to ischemia. In group two, gerbils were treated with TMZ at a dose of 25 mg/kg given intraperitoneally after ischemia. Saline-injected gerbils served as controls. Histological evaluation of neuronal damage was carried out using the silver staining technique in gerbils 4 and 21 days after the start of the experimental protocol. Behavioral functions were assessed in gerbils from the 14th to the 21st day after the start of the experimental protocol using the Morris water maze test. Results obtained from this study showed no significant difference between saline treated TMZ-treated gerbils when TMZ was administered after ischemia. When TMZ was administered prior to ischemia, there was a reduction in neuronal damage although it did not reach statistical significance and a statistically significant improvement in behavior. We conclude that TMZ shows signs of promise as a neuroprotective agent, and further studies should look at pre-treatment with different doses and different times.

Animals↗

PubMed2002

Involvement of inflammatory cytokines in central nervous system injury.

Pro-inflammatory cytokines, interleukin (IL) 1 and tumor necrosis factor (TNF), possess a wide range of biological actions in various tissues. In recent years, there has been increasing evidence that these cytokines are involved in inflammatory reactions in central nervous system (CNS) diseases. Although many studies have demonstrated that IL-1, TNF, and their mRNA are up-regulated in the CNS after injury, the functional roles of these cytokines in the injury are far from completely understood. Overexpression of these cytokines, such as observed during the early stage of injury, can be harmful for the injured tissue. However, low levels of these cytokines, observed during the recovery stage after injury, can enhance repair processes of the injured tissues.

Animals↗

PubMed2002

Adherence to practice guidelines for transient ischemic attacks in an emergency department.

OBJECTIVE: To evaluate the investigation and treatment of patients with a diagnosis of transient ischemic attacks (TIA) in the emergency department (ED) a tertiary care teaching hospital with a neuroscience referral program. METHODS: A chart review was conducted in the hospital. Consecutive ED charts with a diagnosis of TIA were included; each was reviewed by independent coders using a standardized data form. RESULTS: Two hundred and ninety-three TIA charts were reviewed; the gender ratio was 1:1 with a mean age of 66 years. Most patients (75%; 95% CI: 70, 80) were evaluated by ED physicians; the remaining patients were seen directly by referral services. The median time from symptom onset to ED arrival was 29 hours and the duration of symptoms was 4.6 hours. Most patients received CT scans (81%; 95% CI: 73, 85), complete blood counts (74%; 95% CI: 68, 79), and electrocardiograms (75%; 95% CI: 70, 80) in the ED. In 16% (95% CI: 13, 22) a carotid doppler was performed and in 26% (95% CI: 21, 31) an outpatient doppler was booked. Among those who were discharged (75%; 95% CI: 70, 80), antithrombotic medications were not prescribed to 28% (95% CI: 22, 34). CONCLUSION: Practice variation exists with respect to the investigation and treatment of TIAs in this tertiary-care teaching hospital. Carotid doppler investigation and use of anti-platelet therapy for patients with TIA are suboptimal. Clinical practice guidelines and rapid assessment TIA clinics may change these results.

Aged↗

PubMed2002

Glycoprotein IIb/IIIa antagonist, murine 7E3 F(ab') 2, and tissue plasminogen activator in focal ischemia: evaluation of efficacy and risk of hemorrhage with combination therapy.

Tissue hypoperfusion during cerebral ischemia results from occlusion of large and small vessels. Combination treatment strategies using fibrinolytics to thrombolyse an embolic clot and antiplatelet agents to prevent reocclusion and the formation of new platelet thrombi in the microcirculation may offer advantages over single-agent therapy. The authors report on the effects of tissue plasminogen activator (rt-PA), a glycoprotein (GP) IIb/IIIa receptor antagonist, 7E3 F(ab') 2, or a combination of the two agents in a focal embolic model of cerebral ischemia in Wistar rats. Focal ischemia was produced by introducing an autologous thrombus into the right side middle cerebral artery. Forty-six male Wistar rats were randomly divided into 6 groups: control (n = 8), 7E3 F(ab') 2 (n = 9, 6 mg/kg), rt-PA (n = 9, 10 mg/kg), rt-PA (n = 6, 20 mg/kg), and 7E3 F(ab') 2 with either 10 mg/kg (n = 10) (low-dose combination) or 20 mg/kg (n = 6) (high-dose combination) rt-PA. Evaluation of neurobehavioral scores, cerebral angiography, bleeding time, and measurement of brain infarction volume were used to determine efficacy. All actively treated groups showed a significant reduction in the infarct volume. Animals treated with 7E3 F(ab') 2 showed reduced infarction volumes (24.0 +/- 5.1%) compared with controls (42.43 +/- 5.6%, P < 0.02). Treatment with rt-PA significantly reduced infarction volume (20.7 +/- 3.3, = 0.01) at 10 mg/kg and at 20 mg/kg (19.5 +/- 8.2%, P < 0.05). Compared with vehicle-treated animals, the low-dose combination (16.4 +/- 5.5, P < 0.003) and high-dose combination (23.7 +/- 6.2%, P < 0.05) showed significant reduction in infarction volume. Cerebral angiography revealed significantly better recanalization in the combination group (5/6 animals in the high dose and 4/6 in low dose) compared with animals treated with 7E3 F(ab') 2 (3/10) or rt-PA alone (2/6). Bleeding time significantly increased from 11.25 +/- 1.9 minutes in the control group to 17 +/- 3.1 minutes in the rt-PA group, 24.5 +/- 2.6 minutes in the 7E3 F(ab') 2 group, 25.7 +/- 3.1 minutes in the low-dose combination group, and 32.5 +/- 4.7 minutes in the high-dose combination group. The incidence of intercerebral hemorrhage was highest in the high-dose combination group (6 of 6 animals) and lowest in the single treatment with 7E3 F(ab') 2 alone (1 of 10 animals) ( P < 0.05). Our data show that murine 7E3 F(ab') 2 alone has therapeutic effects when used after cerebral ischemia. Although this study suggests that higher doses of thrombolytic combined with anti-GPIIb/IIIa therapy may increases the risk of intracranial hemorrhage, the data also support the notion that anti-GPIIb/IIIa agents can safely be combined with low doses of thrombolytic agent to produce significant attenuation of neuronal damage with no increase in the incidence of cerebral hemorrhage.

Animals↗

PubMed2002

How well are hypertension, hyperlipidemia, diabetes, and smoking managed after a stroke or transient ischemic attack?

BACKGROUND AND PURPOSE: Stroke prevention clinics (SPCs) are not usually involved with the active management of hypertension, hyperlipidemia, diabetes, and smoking. The effect of consultations generated at SPCs on the adequacy of the management of these risk factors for stroke has not been well described, and few studies have long-term follow-up. METHODS: We performed a prospective study of 119 consecutive patients referred to an SPC for secondary prevention. One year after their baseline visit, patients were re-evaluated for the adequacy of the management of the above risk factors, and the proportion of improvement was assessed. RESULTS: One-hundred twelve patients returned for their 1-year follow-up visit. Sixty-six were male, and the average age was 65 years. Hypertension was present in 83 patients, hyperlipidemia in 92, diabetes in 26, and smoking in 38, and 80 had multiple risk factors. At baseline, 66% of patients with hypertension, 17% of patients with hyperlipidemia, and 23% of diabetics had adequate management of their respective risk factors. During 1 year of follow-up, hypertension management improved 20% (P<0.001) and lipid management improved 32% (P<0.001). There was no significant improvement in diabetes management or smoking cessation. CONCLUSIONS: Although our understanding of the benefit of addressing hypertension, hyperlipidemia, diabetes, and smoking for secondary prevention of stroke is evolving, we found marked room for improvement in the management of these four risk factors. SPCs may need to be more actively involved in the management of these modifiable risk factors, if we are to significantly impact the risk of recurrent stroke.

Adult↗

PubMed2002

Effects of nonpeptide V(1) vasopressin receptor antagonist SR-49059 on infarction volume and recovery of function in a focal embolic stroke model.

BACKGROUND AND PURPOSE: Cerebral edema develops very early after the onset of focal cerebral ischemia and may be a major factor in early disability after an acute ischemic stroke. There have been very limited studies on the usefulness of antiedemic agents as neuroprotective agents in the setting of focal cerebral ischemia. We tested the neuroprotective effects of a new potent nonpeptide vasopressin receptor V(1) antagonist, SR-49059, in a focal embolic stroke model in rats. METHODS: Focal ischemic injury was induced by embolizing a preformed clot into the middle cerebral artery (MCA). Infarction volume was measured at 48 hours after the MCA occlusion. Neurological deficits, ischemic brain edema, seizure activity, and mortality and hemorrhage rates were also documented. RESULTS: Treatment with SR-49059 (2 mg/kg), initiated immediately after MCA occlusion, significantly reduced infarction volume (P<0.05) measured at 48 hours after the arterial occlusion. In animals in which the treatment was delayed for 1 hour after MCA occlusion, infarction volume was also reduced significantly (P<0.05). Infarction volume in the rats that received the drug at 3 or 6 hours after MCA occlusion was not different from that in the vehicle-treated group. Treatment with SR-49059, when started early after the arterial occlusion, also reduced neurological deficits and ischemic brain edema. Injection of drug at a higher dose (30 mg/kg) also reduced infarction volume and improved functional recovery but was not superior to the lower dose (2 mg/kg) when the drug was administrated at 1 hour after MCA occlusion. CONCLUSIONS: Our data show that the selective vasopressin receptor antagonist SR-49059 is a potent neuroprotective agent when used early after onset of arterial occlusion in an embolic focal ischemia model in rats. Further studies are needed in stroke models to better understand its neuroprotective properties when used alone or in combination with thrombolysis.

Animals↗

PubMed2002

Turbulence and circulating cerebral emboli detectable at Doppler ultrasonography: a differentiation study in a stenotic middle cerebral artery model.

BACKGROUND AND PURPOSE: Blood flow within the middle cerebral artery can be monitored by transcranial Doppler (TCD) ultrasonography. Arterial stenosis can produce turbulent flow, but controversy remains regarding the degree of stenosis needed to cause TCD-detectable turbulence. Furthermore, cerebral emboli and turbulent flow may coexist in the same patient. The current study was designed to study the relationship between stenotic degree and TCD-detectable turbulent flow and its differentiation from cerebral emboli. METHODS: A stenotic middle cerebral artery model was constructed to allow the study of different degrees of stenosis. TCD was used to detect the turbulent flow and embolic materials in the circulation model, and signal intensities were analyzed. RESULTS: Turbulent flow was generated with a series of short, asymmetric stenoses in this test. Transition of turbulence from laminar flow began to occur at a moderate degree of stenosis (55% reduction of cross-sectional area) but became dampened at the high degrees of stenoses (>/=75%). Turbulence caused a notable increase in average Doppler signal intensity. However, the degree of stenosis was not associated with signal intensity at the region where turbulence existed, but rather was related to the mean flow velocity measured at the narrowed region. Embolic materials such as air bubbles (30 micro m) and platelet-rich clots (100 micro m) had notably higher Doppler signal intensity than that produced by turbulence. CONCLUSION: TCD-detectable turbulence predominantly developed at a moderate arterial stenosis and its acoustic signature with TCD is different from that caused by air bubbles and platelet-rich clots.

Blood Flow Velocity↗

PubMedDate not supplied

Clot fragments formed from original thrombus obstruct downstream arteries in the ischemic injured brain.

OBJECTIVE: Embolic occlusion of the middle cerebral artery (MCA) leads to distal perfusion deficits as the vessel is recanalized. However, the mechanism for the perfusion deficits is not fully understood. The authors examined whether distal movement of fragments formed from the original thrombus contributes to the perfusion deficits. METHODS: In the first series, they studied whether the reduction in perfusion deficits is due to the dissolution of the original clots embolized or due to collateral perfusion. In the second series, they studied whether fragments formed from the original clots move to distal arterial system. In the third series, they studied whether plasminogen activator plays a role in the thrombolysis following ischemia. RESULTS: Occlusion of MCA permanently resulted in large perfusion deficits in the ipsilateral hemisphere, and these perfusion deficits did not change significantly after the occlusion. In contrast, perfusion deficits reduced significantly in a model of transient MCA occlusion. The numbers of fragments formed from the original clots increased gradually after the MCA occlusion in the ischemic injured brain. In addition, expression of urokinase plasminogen activator was also upregulated. CONCLUSION: The present study thus reveals the mechanisms of the downstream arterial occlusion following the dissolution of original thrombus.

Animals↗