Role of MTHFR C677T polymorphism in ischemic stroke.

BACKGROUND: Homozygosity for MTHFR C677T polymorphism can lead to significantly high homocysteine levels and hyperhomocysteinemia is an important risk factor for thrombotic events. AIMS: The aim was to determine role of MTHFR C677T polymorphism in North Indians with ischemic stroke. SETTINGS AND DESIGN: In a prospective study, the subjects of stroke were recruited from the neurology clinic of the hospital. Controls were healthy individuals from the Hematology clinic without any history of stroke. MATERIALS AND METHODS: Plasma homocysteine levels were measured by enzyme immuno assay method after 3 months of acute episode. Serum folate and Vitamin B12 levels were estimated by competitive inhibition radioassay. MTHFR polymorphism was detected by PCR-RFLP using Hinf I enzyme. Statistical analysis: The analysis of significance of results was done using SPSS software package. A p-value. RESULTS: Thirty-two acute ischemic stroke patients (aged 1-44 years) were studied. Fourteen (43.8%) had recurrent stroke. Nine (28%) had multiple infarcts. Four of 32 patients (12.5%) had high homocysteine levels. Three out of these 4 hyper-homocysteinemia patients were homozygous ( TT ) for MTHFR polymorphism (2 with recurrent stroke). Two of three homozygous cases with TT genotype had low serum folate. Five of 32 stroke cases (18.8%) were heterozygous ( CT ) genotype. CONCLUSIONS: Primary hyper-homocysteinemia appears to be an important risk factor for ischemic stroke in North Indians, most due to MTHFR C677T homozygosity. Folate levels may modify the presentation of the MTHFR TT genotype.

Atontamiento miocardico luego del accidente cerebrovascular isquemico / Stunned myocardium after acute ischemic stroke

El atontamiento miocárdico, definido como una disfunción contráctil transitoria del miocardio, ha sido demostrado claramente en distintas situaciones clínicas. Sin embargo, el atontamiento miocárdico asociado a un accidente cerebrovascular isquémico ha sido escasamente notificado. Describiremos dos pacientes con diagnóstico de accidente cerebrovascular isquémico agudo que presentaron cambios electrocardiográficos, elevación enzimática y trastornos en la motilidad cardíaca, compatibles con disfunciónmiocárdica. Simultáneamente desarrollaron injuria pulmonar aguda rápidamente reversible, originada probablemente por un doble componente neuro-cardiogénico.

The so-called stunned myocardium, defined as transitory myocardial contractile dysfunction, has been clearly demonstrated in diverse clinical situations. However, stunned myocardium related to ischemic stroke has been poorly identified. We describetwo patients with diagnosis of acute ischemic stroke who developed elctrocardiographic changes, cardiac enzyme increasing levels and myocardial dysfunction secondary to abnormal cardiac wall motion. At the same time the patients developed acute lung injury with rapid resolution, perhaps as a consequence of neurocardiogenic components.

Brain ischemia alters platelet ATP diphosphohydrolase and 5'-nucleotidase activities in naive and preconditioned rats

The effects of transient forebrain ischemia, reperfusion and ischemic preconditioning on rat blood platelet ATP diphosphohydrolase and 5'-nucleotidase activities were evaluated. Adult Wistar rats were submitted to 2 or 10 min of single ischemic episodes, or to 10 min of ischemia 1 day after a 2-min ischemic episode (ischemic preconditioning) by the four-vessel occlusion method. Rats submitted to single ischemic insults were reperfused for 60 min and for 1, 2, 5, 10 and 30 days after ischemia; preconditioned rats were reperfused for 60 min 1 and 2 days after the long ischemic episode. Brain ischemia (2 or 10 min) inhibited ATP and ADP hydrolysis by platelet ATP diphosphohydrolase. On the other hand, AMP hydrolysis by 5'-nucleotidase was increased after 2, but not 10, min of ischemia. Ischemic preconditioning followed by 10 min of ischemia caused activation of both enzymes. Variable periods of reperfusion distinctly affected each experimental group. Enzyme activities returned to control levels in the 2-min group. However, the decrease in ATP diphosphohydrolase activity was maintained up to 30 days of reperfusion after 10-min ischemia. 5'-Nucleotidase activity was decreased 60 min and 1 day following 10-min ischemia; interestingly, enzymatic activity was increased after 2 and 5 days of reperfusion, and returned to control levels after 10 days. Ischemic preconditioning cancelled the effects of 10-min ischemia on the enzymatic activities. These results indicate that brain ischemia and ischemic preconditioning induce peripheral effects on ecto-enzymes from rat platelets involved in nucleotide metabolism. Thus, ATP, ADP and AMP degradation and probably the generation of adenosine in the circulation may be altered, leading to regulation of microthrombus formation since ADP aggregates platelets and adenosine is an inhibitor of platelet aggregation

Immunocytochemical distribution of gamma isoform of protein kinase C (PKC-gamma) following incomplete ischaemia.

Immunocytochemical distribution of PKC-gamma was examined in rat brain in relation to molecular mechanisms of post-ischaemic neuronal modulation following incomplete ischaemia. Incomplete ischaemia was developed by either permanent occlusion of one common carotid artery (CA) or permanent occlusion of one CA with temporary occlusion of opposite CA. Unilateral CA (UCA) occlusion resulted in a pronounced increase in the intensity of staining and number of PKC-gamma positive neurons in the neocortex ipsilateral to the insult after 3 h. The effect was maximum at 6-12 h and was undetectable after 7 days. CA1 neurons showed an increase immunoreactivity (IR) after 1 day, reached to a peak by 3 days, then reduced to basal levels after 7 days. Bilateral CA (BCA) occlusion showed almost similar changes in the neocortex, but on both sides and short durated. The altered patterns of PKC-gamma IR in the neocortex and hippocampus following CA occlusion may reflect activation and/or down-regulation of PKC-gamma in ischaemic neurons. PKC-gamma may, therefore, potentially play an important role in the post-ischaemic modulation of synaptic efficacy in these neurons and in the neuronal damage following incomplete ischaemia.