Doble terapia antiagregante en pacientes con accidente cerebrovascular isquémico agudo: Recomendación del grupo CIERTO / Dual antiplatelet therapy for secondary stroke prevention in patients with acute ischemic stroke. CIERTO group recommendation

El inicio precoz del tratamiento con antiagregantes plaquetarios es considerado el estándar de cuidado para pacientes con accidente cerebrovascular isquémico agudo. Distintos esquemas de antiagregación se han comparado con resultados que sugieren que la combinación de múltiples antiagregantes se asocian a menor riesgo de recurrencia de accidente cerebrovascular (ACV) pero a expensas de un aumento en el riesgo de sangrado, lo que a largo plazo termina opacando dichos beneficos. Sin embargo, considerando que el riesgo de recurrencia de ACV es mayor en el periodo inmediato al evento, la indicación de doble tratamiento antiagregante por tiempos limitados podría asociarse a beneficios relevantes. Con este concepto, se realizó una revisión sistemática rápida con el objetivo de evaluar el efecto del tratamiento con doble antiagregación por un periodo corto intentando maximizar el beneficio y reducir al mínimo el riesgo de sangrado. Se incluyeron todos los estudios primarios identificados en los que se comparó un esquema de doble antiagregación, iniciado en el periodo agudo del evento índice (ACV o accidente isquémico transitorio - AIT), contra un esquema de simple antiagregación. El cuerpo de la evidencia mostró que la intervención (doble antiagregación) reduce el riesgo de recurrencia de ACV y probablemente se asocie a un aumento marginal en el riesgo de sangrado mayor. Sugerimos indicar doble esquema antiplaquetario para el tratamiento inicial de pacientes con ACV isquémico menor (Score NIH < o igual a 3 o AIT).

One of the main pillars of acute ischemic stroke management is antiplatelet therapy. Different treatment schemes have been compared, suggesting that the combination of multiple antiplatelet drugs is associated with a reduced risk of stroke recurrence. However, it has also been associated with an increased risk of bleeding complications which, in the long term, surpass the mentioned benefits. However, considering that most stroke recurrences occur i n the short term, a time limited double antiplatelet scheme could result in significant benefits to patients with acute ischemic stroke. On this basis, we conducted a rapid systematic review of the literature in order to evaluate the effects of a short-term double antiplatelet therapy both on stroke recurrence and complications. All trials comparing double versus single antiplatelet therapy in patients with acute ischemic stroke were included. Results showed that double therapy reduces recurrence risk but probably marginally increases major bleeding complications. We suggest double antiplatelet therapy for the initial management of patients with minor (Score NIH < or equal to 3 or transient isquemic attack -TIA) acute ischemic stroke.

Pre, intra and post-ischemic hypothermic neuroprotection in temporary focal cerebral ischemia in rats: morphometric analysis / Neuroproteção hipotérmica pré, intra e pós-isquêmica na isquemia cerebral focal temporária em ratos: análise morfométrica

OBJECTIVE: To evaluate the neuroprotection of mild hypothermia, applied in different moments, in temporary focal cerebral ischemia in rats. METHODS: Rats was divided into Control (C), Sham (S), Ischemic-control(IC), Pre-ischemic Hypothermia (IH1), Intra-ischemic Hypothermia (IH2), and Post-ischemic Hypothermia (IH3) groups. Morphometry was performed using the KS400 software (Carl Zeiss®) in coronal sections stained by Luxol Fast Blue. Ischemic areas and volumes were obtained. RESULTS: Statistically, blue areas showed difference for C vs. IC, IC vs. IH1 and IC vs. IH2 (p=0.0001; p=0.01; p=0.03), and no difference between C vs. S, IC vs. IH3 and IH vs. IH2 (p=0.39; p=0.85; p=0.63). Red areas showed difference between C vs. IC, IC vs. IH1 and IC vs. IH2 (p=0.0001; p=0.009; p=0.03), and no difference between C vs. S, IC vs. IH3 and IH1 vs. IH2 (p=0.48; p=0.27; p=0.68). Average ischemic areas and ischemic volumes showed difference between IC vs. IH1 and IC vs. IH2 (p=0.0001 and p=0.0011), and no difference between IC vs. IH3 and IH1 vs. IH2 (p=0.57; p=0.79). CONCLUSION: Pre-ischemic and intra-ischemic hypothermia were shown to be similarly neuroprotective, but this was not true for post-ischemic hypothermia.

OBJETIVO: Avaliar a neuroproteção da hipotermia leve, aplicada em diferentes momentos, durante isquemia cerebral focal temporária em ratos. MÉTODOS: Ratos foram divididos em grupos: Controle (C), Sham (S), Controle-isquêmico (IC), Hipotermia Pré-isquêmica (IH1), Hipotermia Intra-isquêmica (IH2) e Hipotermia Pós-isquêmica (IH3). A morfometria foi realizada em secções coronais coradas por Luxol Fast Blue através do programa KS400 (Carl Zeiss®). Foram calculados áreas e volumes isquêmicos. RESULTADOS: Estatisticamente, áreas azuis demonstraram diferença entre os grupos C vs. IC, IC vs. IH1 e IC vs. IH2 (p=0,0001; p=0,01; p=0,03), e nenhuma diferença entre C vs. S, IC vs. IH3 e IH vs. IH2 (p=0,39; p=0,85; p=0,63). Áreas vermelhas demonstraram diferença entre C vs. IC, IC vs. IH1 e IC vs. IH2 (p=0,0001; p=0,009; p=0,03), e nenhuma diferença entre C vs. S, IC vs. IH3 e IH1 vs. IH2 (p=0,48; p=0,27; p=0,68). Áreas isquêmicas médias e volumes isquêmicos demonstraram diferença entre os grupos IC vs. IH1 e IC vs. IH2 (p=0,0001 and p=0,0011), e nenhuma diferença entre IC vs. IH3 and IH1 vs. IH2 (p=0,57; p=0,79). CONCLUSÃO: Hipotermias pré-isquêmica e intra-isquêmica demonstraram neuroproteção em grau semelhante, o que não ocorreu com hipotermia pós-isquêmica.

Protective effect of Yulangsan polysaccharide on focal cerebral ischemia/reperfusion injury in rats and its underlying mechanism

To study the focal cerebral ischemia/reperfusion [I/R] injury induced by a middle cerebral artery occlusion [MCAO], and the effects of Yulangsan [YLS] polysaccharide on this injury. This study took place in the Pharmacology Research Laboratory at Guangxi Medical University, China, between March and May 2007. Two hundred and forty rats were randomly divided into I/R group, sham-operated group, high-, medium-, and low-dose of YLS polysaccharide groups, and nimodipine [Nim] group. The animals were intragastrically administered with drugs for 7 days. An operation was performed to induce an MCAO model in the rats. Reperfusion was started after 2 hours of MCAO. The influences of YLS polysaccharide on the neurological score, the brain water content, the infarct volume, the activities of super oxide dismutase [SOD] and nitric oxide synthase [NOS], the contents of malondialdehyde [MDA] and nitric oxide [NO], the expressions of B-cell lymphoma/leukemia-2 [Bcl-2] and Bcl-2-associated X protein [Bax] in brain tissue were investigated; the morphological changes of rat cerebral cortical neurons were observed. Compared with the I/R group, YLS polysaccharide reduced the neurological score, the brain water content, the infract volume, MDA and NO contents, the NOS activity, and the expression of Bax, and increased SOD activity, and the expression of Bcl-2 in the brain tissue, and neuronal edema was reduced. The YLS polysaccharide has a protective effect on cerebral ischemia/reperfusion injury; the mechanism may be related to attenuating free radicals, and increasing the Bcl-2/Bax ratio

Progesterone: Protective effects on the cat hippocampal neuronal damage due to acute global cerebral ischemia

Background. Barbiturates, benzodiazepines, and synthetic steroids having anesthetic properties, by enchacing the inhibitory GABAergic neurotransmission to the neruronal circuits of cerebral structures vulnerable to ischemia, reduce the damage induced by this condition. Some endogenous steroids resulting from progesterone (P4) biotransformation in the brain exert GABAaergic effects, thus inhibiting neuronal excitability. Hence, P4 administration both before and after an experimentally induced ischemic episode may prevent or decrease the ischemic cerebral damage. Methods. Ovariectomized adult cats were treated sc with either P4 (10 mg/kg/day) or corn oil during 7 days before and 7 days after being subjected to a period of acute global cerebral ischemia by 15 min of cardiorespiratory arrest followed by 4 min of reanimation. After 14 days of survival, animals were sacrificed and the brains perfused in situ and formalin-fixed for histological examination. Results. Acute global cerebral ischemia resulted in a severe loss of neurons (54-85 percent), mainly in CA1 and CA2 subfields of oil-treated cats. Progesterone significantly reduced the neuronal loss in those areas (21-49 percent). Conclusions. Overall results suggest that progesterone exerts protective effects against the neuronal cerebral damage induced by acute global cerebral ischemia

Clinical Trial of a Calcium Channel Blocker in Patients with Aneurysmal Subarachnoid Hemorrhage

Forty-three patients with aneurysmal subarachnoid hemorrhage entered a nimodipine trial in the Department of Neurosurgery, Yonsei university to determine the efficacy of the drug in preventing vasospasm and to evaluate the tolerability of this calcium channel blocker. Thirty-three patients completed the study. Treatment was started within four days of initial bleeding and continued for two weeks. Delayed neurological deficits developed in seven of the 33 patients-four from vasospasm, two from elevated intracranial pressure, and one from recurrent bleeding. The incidence of symptomatic vasospasm which developed after calcium channel blocker (nimodipine) treatment was 12.1%, which is about one third of the rate experienced at our department during the past five years (33.2%). Twenty-five patients were operated on without surgical mortality and the morbidity rate was 8%. Side effects due to nimodipine treatment were reversible and insignificant. This study suggests that treatment with a calcium channel blocker that has a selective cerebrovascular effect may prevent or reduce the incidence of delayed ischemic deficits in patients with aneurysmal subarachnoid hemorrhage.