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  1. Putteeraj M, Lim WL, Teoh SL, Yahaya MF
    Curr Drug Targets, 2018;19(14):1710-1720.
    PMID: 29577854 DOI: 10.2174/1389450119666180326125252
    Brain ischemia is among the leading cause of death with majority of the cases are associated with ischemic strokes. It can occur in two forms of either focal or global ischemia. Neurodegenerative disorder such as Alzheimer and Parkinson diseases is also on the rise worldwide. These disorders have common similarities; i.e. they all affecting the central nervous system with debilitating effect to the patient. In this review, we look into the promising role of flavonoids, a natural bioactive compound found abundant in vegetables, fruits and traditional herbs. Treatment with flavonoids such as curcumin, lycopene, ginsenoside, vitexin and baicalin have shown promising neuroprotective effects against ischemic-induced injury. Besides anticancer, antioxidant and immunomodulation properties, flavonoid also exerts neuroprotective effects by increases neuronal viability, increases tissue perfusion and cerebral blood flow and reduce ischemic-related apoptosis. In addition, flavonoid also exerts anti-amyloidogenic effect and reduces loss of dopaminergic neurons in the brain. These results suggesting flavonoids might be able to serve as a potential therapeutic agent in brain disorders.
    Matched MeSH terms: Brain Ischemia/drug therapy*
  2. Hassan Y, Al-Jabi SW, Aziz NA, Looi I, Zyoud SH
    Int J Clin Pharmacol Ther, 2011 Oct;49(10):605-13.
    PMID: 21961485 DOI: 10.5414/cp201574
    BACKGROUND: Patients with diabetes mellitus (DM) are more prone to develop atherosclerotic complications including stroke. Moreover, as a primary and secondary prevention of stroke, antiplatelet therapy is recommended by clinical guidelines for patients with DM.

    AIMS: This study aimed to determine the prevalence of antiplatelet therapy use prior to current stroke in diabetic ischemic stroke patients, to examine the factors associated with the use of this important therapy and to assess the impact of the previous use of antiplatelet therapy on ischemic stroke outcomes.

    METHODS: An observational study of diabetic acute ischemic stroke patients attending a Malaysian hospital during a 1-year period was carried out. Demographic information, risk factors, previous antiplatelet use and variables used to assess stroke outcomes were collected from medical records.

    RESULTS: Overall, 295 diabetic stroke patients were analyzed. The prevalence of previous antiplatelet use among diabetic patients was 38.3%. The independent variables associated with the previous use of antiplatelet medication were previous stroke attack (p < 0.001) and ischemic heart disease (p < 0.001). Better outcomes as measured by a minor Glasgow Coma Scale at admission (p = 0.032), and a higher Modified Barthel index at discharge (p = 0.027) were observed among patients on previous antiplatelet therapy.

    CONCLUSION: Our data suggest that antiplatelet therapy is under prescribed among such diabetic stroke patients, particularly in primary prevention. Effective methods to increase antiplatelet use and to enhance the adherence of clinical practice guidelines should be considered at the national and community level.
    Matched MeSH terms: Brain Ischemia/drug therapy*
  3. Hwong WY, Abdul Aziz Z, Sidek NN, Bots ML, Selvarajah S, Kappelle LJ, et al.
    BMC Neurol, 2017 Nov 23;17(1):203.
    PMID: 29169331 DOI: 10.1186/s12883-017-0984-1
    BACKGROUND: Evaluation of secondary stroke prevention in low and middle-income countries remains limited. This study assessed the prescription of secondary preventive drugs among ischemic stroke patients upon hospital discharge in Malaysia and identified factors related to the prescribing decisions.

    METHODS: From Malaysian National Stroke Registry, we included patients with non-fatal ischemic stroke. Prescriptions of antiplatelet, anticoagulants, antihypertensive drugs and lipid-lowering drugs were assessed. Multi-level logistic regressions were performed to determine the relation between potential factors and drug prescriptions.

    RESULTS: Of 5292 patients, 48% received antihypertensive drugs, 88.9% antiplatelet and 88.7% lipid-lowering drugs upon discharge. Thirty-three percent of patients with an indication for anticoagulants (n = 391) received it. Compared to patients <=50 years, patients above 70 years were less likely to receive antiplatelet (OR: 0.72, 95% CI: 0.50-1.03), lipid-lowering drugs (OR: 0.66, 95% CI: 0.45-0.95) and anticoagulants (OR: 0.27, 95% CI: 0.09-0.83). Patients with moderate to severe disability upon discharge had less odds of receiving secondary preventive drugs; an odds ratio of 0.57 (95% CI: 0.45-0.71) for antiplatelet, 0.86 (95% CI: 0.75-0.98) for antihypertensive drugs and 0.78 (95% CI: 0.63-0.97) for lipid-lowering drugs in comparison to those with minor disability. Having prior specific comorbidities and drug prescriptions significantly increased the odds of receiving these drugs. No differences were found between sexes and ethnicities.

    CONCLUSIONS: Prescription of antihypertensive drugs and anticoagulants among ischemic stroke patients in Malaysia were suboptimal. Efforts to initiate regular clinical audits to evaluate the uptake and effectiveness of secondary preventive strategies are timely in low and middle-income settings.

    Matched MeSH terms: Brain Ischemia/drug therapy*
  4. Hassan Y, Al-Jabi SW, Aziz NA, Looi I, Zyoud SH
    Clin Neuropharmacol, 2011 Nov-Dec;34(6):234-40.
    PMID: 21996648 DOI: 10.1097/WNF.0b013e3182348abe
    BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs), antiplatelets (APs), and statin are increasingly being prescribed for ischemic stroke prevention.
    OBJECTIVES: The objective of the study was to examine whether previous combination therapy of ACEI with AP and/or statin has additive effect compared with ACEI alone on functional outcome after ischemic stroke. Furthermore, factors associated with improving functional outcome were investigated.
    METHODS: Ischemic stroke patients attending a Malaysian hospital in 2008 were categorized according to Barthel Index at discharge. Favorable outcome was defined as Barthel Index of 75 or greater. Data included demographic information, clinical characteristics, and previous medications with particular attention to ACEI, AP, and statin.
    RESULTS: Overall, 505 patients were included. Variables associated with good functional outcome were younger age (P = 0.002), first-ever attack (P = 0.016), lacunar (P = 0.015) or posterior circulation infarct stroke subtype (P = 0.034), minor Glasgow Coma Scale (P < 0.001), and previous use of ACEI alone or combined with AP and/or statin (P = 0.002). Using ACEI alone as the reference for ACEI + AP, ACEI + statin, or ACEI + AP + statin combinations, there was no significant difference among combinations on improving functional outcome (P = 0.852).
    CONCLUSIONS: Prestroke use of ACEI either alone or combined with AP and/or statin was associated with better functional outcome. Previous use of ACEI in combination with AP and/or statin did not significantly differ from ACEI alone in their effect on outcome. Our study provides a potential rationale for optimizing the use of ACEI among individuals at risk of developing ischemic stroke.
    Matched MeSH terms: Brain Ischemia/drug therapy*
  5. Damodaran T, Tan BWL, Liao P, Ramanathan S, Lim GK, Hassan Z
    J Ethnopharmacol, 2018 Oct 05;224:381-390.
    PMID: 29920356 DOI: 10.1016/j.jep.2018.06.020
    ETHNOPHARMACOLOGICAL RELEVANCE: Clitoria ternatea L. (CT), commonly known as Butterfly pea, is used in Indian Ayurvedic medicine to promote brain function and treat mental disorders. Root of CT has been proven to enhance memory, but its role in an animal model of chronic cerebral hypoperfusion (CCH), which has been considered as a major cause of brain disorders, has yet to be explored.

    AIM OF THE STUDY: To assess the motor and cognitive effects of acute oral administration of CT root methanolic extract and hippocampal long-term plasticity in the CA1 region of the CCH rat model.

    MATERIALS AND METHODS: Male Sprague Dawley rats (200-300 g) were subjected to permanent bilateral occlusion of common carotid arteries (PBOCCA) or sham operation. Then, these rats were given oral administration of CT root extract at doses of 100, 200 or 300 mg/kg on day 28 post-surgery and tested using behavioural tests (open-field test, passive avoidance task, and Morris water maze) and electrophysiological recordings (under urethane anaesthesia).

    RESULTS: Treatment with CT root extract at the doses of 200 and 300 mg/kg resulted in a significant enhancement in memory performance in CCH rats induced by PBOCCA. Furthermore, CCH resulted in inhibition of long-term potentiation (LTP) formation in the hippocampus, and CT root extract rescued the LTP impairment. The CT root extract was confirmed to improve the glutamate-induced calcium increase via calcium imaging using primary cultured rat neurons. No significance difference was found in the CaMKII expression. These results demonstrated that CT root extract ameliorates synaptic function, which may contribute to its improving effect on cognitive behaviour.

    CONCLUSIONS: Our findings demonstrated an improving effect of CT root extract on memory in the CCH rat model suggesting that CT root extract could be a potential therapeutic strategy to prevent the progression of cognitive deterioration in vascular dementia (VaD) and Alzheimer's disease (AD) patients.

    Matched MeSH terms: Brain Ischemia/drug therapy*
  6. Tai MLS, Goh KJ, Kadir KAA, Zakaria MI, Yap JF, Tan KS
    Singapore Med J, 2019 May;60(5):236-240.
    PMID: 30488077 DOI: 10.11622/smedj.2018150
    INTRODUCTION: Intravenous (IV) thrombolysis with alteplase (rt-PA) is effective in ischaemic stroke. The primary objective was to evaluate predictors of functional outcome in acute ischaemic stroke (AIS) patients treated with IV rt-PA. The secondary objective was to assess the outcome with the modified Rankin scale (mRS). We also examined the predictive value of the Totaled Health Risks in Vascular Events (THRIVE) score.

    METHODS: AIS patients treated with IV rt-PA from February 2012 to August 2016 were recruited. Demographic data, National Institutes of Health Stroke Scale (NIHSS) scores, timing and neuroradiological findings were recorded. Patients received a dose of 0.9 mg/kg IV rt-PA within 4.5 hours of symptom onset. mRS score was evaluated at discharge and three months, and good and poor clinical outcomes were defined as scores of 0-2 and 3-6, respectively. Baseline THRIVE scores were assessed.

    RESULTS: 36 patients received IV rt-PA. 20 (55.6%) patients had an mRS score of 0-2 at three months. Based on THRIVE score, 86.1% had a good or moderately good prognosis. On univariate analysis, poor outcome was associated with NIHSS score before rt-PA (p = 0.03), THRIVE score (p = 0.02), stroke subtype (p = 0.049) and diabetes mellitus (DM; p = 0.06). Multiple logistic regression showed that outcome was significantly associated with NIHSS score before rt-PA (p = 0.032) and DM (p = 0.010).

    CONCLUSION: Our newly developed Malaysian IV rt-PA service is safe, with similar outcomes to the published literature. Functional outcome after thrombolysis was associated with baseline NIHSS score and DM.

    Matched MeSH terms: Brain Ischemia/drug therapy*
  7. Hassan Y, Al-Jabi SW, Aziz NA, Looi I, Zyoud SH
    Basic Clin Pharmacol Toxicol, 2012 Apr;110(4):370-7.
    PMID: 22023326 DOI: 10.1111/j.1742-7843.2011.00825.x
    There has been recent interest in combining antiplatelets, angiotensin-converting enzyme inhibitors (ACEIs) and statins in primary and secondary ischaemic stroke prevention. This observational study was performed to evaluate the impact of adding ACEIs and/or statins to antiplatelets on post-stroke in-hospital mortality. Ischaemic stroke patients attending a hospital in Malaysia over an 18-month period were evaluated. Patients were categorized according to their vital status at discharge. Data included demographic information, risk factors, clinical characteristics and previous medications with particular attention on antiplatelets, ACEIs and statins. In-hospital mortality was compared among patients who were not taking antiplatelets, ACEIs or statins before stroke onset versus those who were taking antiplatelets alone or in combination with either ACEIs, statins or both. Data analysis was performed using SPSS version 15. Overall, 637 patients met the study inclusion criteria. After controlling for the effects of confounders, adding ACEIs or statins to antiplatelets significantly decreased the incidence of death after stroke attack by 68% (p = 0.036) and 81% (p = 0.010), respectively, compared to patients on antiplatelets alone or none of these medications. Additionally, the addition of both ACEIs and statins to antiplatelet medication resulted in the highest reduction (by 94%) of the occurrence of death after stroke attack (p < 0.001). Our results suggest that adding ACEIs and/or statins to antiplatelets for patients at risk of developing stroke, either as a primary or as a secondary preventive regimen, was associated with a significant reduction in the incidence of mortality after ischaemic stroke than antiplatelets alone. These results might help reduce the rate of ischaemic stroke morbidity and mortality by enhancing the application of specific therapeutic and management strategies for patients at a high risk of acute stroke.
    Matched MeSH terms: Brain Ischemia/drug therapy
  8. Hassan Y, Al-Jabi SW, Aziz NA, Looi I, Zyoud SH
    Fundam Clin Pharmacol, 2011 Jun;25(3):388-94.
    PMID: 20608996 DOI: 10.1111/j.1472-8206.2010.00846.x
    Statins can reduce the risk of stroke in at-risk populations and improve survival after acute ischemic stroke (AIS) among patients with previous statin use. This study aimed to investigate the impact of statin use before AIS onset on in-hospital mortality and identify the factors related to in-hospital mortality among patients with and without previous statin use. A retrospective cohort study of all patients with AIS attending hospital from June 1, 2008 to December 31, 2008. Data were collected from medical records including demographic information, diagnostic information, risk factors, previous statin use, and vital discharge status. Chi-square, Fisher's exact tests, student's t-test, and Mann-Whitney U test, whatever appropriate, were used to test the significance between the variables, and multiple logistic regression was used to identify factors associated with in-hospital mortality. Altogether, 386 patients with AIS were studied, of which 113 (29.3%) had a documented previous statin use. A total of 62 (16.1%) patients with AIS died in hospital. In-hospital mortality was significantly lower among previous statin users (P = 0.013). The presence of atrial fibrillation (AF) increased in-hospital mortality among patients with or without previous statin use. The independent predictors for in-hospital mortality among AIS patients without previous statin use were the presence of diabetes mellitus (P = 0.047), AF (P = 0.045), and renal impairment (P < 0.001). The prophylactic administration of statins significantly reduces post-AIS in-hospital mortality. Furthermore, the identification of predictors of in-hospital mortality might reduce death rates and enhance the application of specific therapeutic and management strategies to patients at a high risk of dying.
    Matched MeSH terms: Brain Ischemia/drug therapy
  9. Hwong WY, Bots ML, Selvarajah S, Abdul Aziz Z, Sidek NN, Spiering W, et al.
    PLoS One, 2016;11(11):e0166524.
    PMID: 27846309 DOI: 10.1371/journal.pone.0166524
    BACKGROUND: The increase in angiotensin II (Ang II) formation by selected antihypertensive drugs is said to exhibit neuroprotective properties, but this translation into improvement in clinical outcomes has been inconclusive. We undertook a study to investigate the relationship between types of antihypertensive drugs used prior to a stroke event and ischemic stroke severity. We hypothesized that use of antihypertensive drugs that increase Ang II formation (Ang II increasers) would reduce ischemic stroke severity when compared to antihypertensive drugs that suppress Ang II formation (Ang II suppressors).

    METHODS: From the Malaysian National Neurology Registry, we included hypertensive patients with first ischemic stroke who presented within 48 hours from ictus. Antihypertensive drugs were divided into Ang II increasers (angiotensin-I receptor blockers (ARBs), calcium channel blockers (CCBs) and diuretics) and Ang II suppressors (angiotensin-converting-enzyme inhibitors (ACEIs) and beta blockers). We evaluated stroke severity during admission with the National Institute of Health Stroke Scale (NIHSS). We performed a multivariable logistic regression with the score being dichotomized at 15. Scores of less than 15 were categorized as less severe stroke.

    RESULTS: A total of 710 patients were included. ACEIs was the most commonly prescribed antihypertensive drug in patients using Ang II suppressors (74%) and CCBs, in patients prescribed with Ang II increasers at 77%. There was no significant difference in the severity of ischemic stroke between patients who were using Ang II increasers in comparison to patients with Ang II suppressors (OR: 1.32, 95%CI: 0.83-2.10, p = 0.24).

    CONCLUSION: In our study, we found that use of antihypertensive drugs that increase Ang II formation was not associated with less severe ischemic stroke as compared to use of antihypertensive drugs that suppress Ang II formation.

    Matched MeSH terms: Brain Ischemia/drug therapy*
  10. Bhuvanendran S, Bakar SNS, Kumari Y, Othman I, Shaikh MF, Hassan Z
    Sci Rep, 2019 10 10;9(1):14507.
    PMID: 31601902 DOI: 10.1038/s41598-019-50954-y
    Alzheimer's disease (AD) is the second most occurring neurological disorder after stroke and is associated with cerebral hypoperfusion, possibly contributing to cognitive impairment. In the present study, neuroprotective and anti-AD effects of embelin were evaluated in chronic cerebral hypoperfusion (CCH) rat model using permanent bilateral common carotid artery occlusion (BCCAO) method. Rats were administered with embelin at doses of 0.3, 0.6 or 1.2 mg/kg (i.p) on day 14 post-surgery and tested in Morris water maze (MWM) followed by electrophysiological recordings to access cognitive abilities and synaptic plasticity. The hippocampal brain regions were extracted for gene expression and neurotransmitters analysis. Treatment with embelin at the doses of 0.3 and 0.6 mg/kg significantly reversed the spatial memory impairment induced by CCH in rats. Embelin treatment has significantly protected synaptic plasticity impairment as assessed by hippocampal long-term potentiation (LTP) test. The mechanism of this study demonstrated that embelin treatment alleviated the decreased expression of BDNF, CREB1, APP, Mapt, SOD1 and NFκB mRNA levels caused by CCH rats. Furthermore, treatment with embelin demonstrated neuromodulatory activity by its ability to restore hippocampal neurotransmitters. Overall these data suggest that embelin improve memory and synaptic plasticity impairment in CCH rats and can be a potential drug candidate for neurodegenerative disease-related cognitive disorders.
    Matched MeSH terms: Brain Ischemia/drug therapy*
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