Reprint of: Fibrinolytic and Non-fibrinolytic Roles of Tissue-type Plasminogen Activator in the Ischemic Brain.

The neurovascular unit (NVU) is assembled by endothelial cells (ECs) and pericytes, and encased by a basement membrane (BM) surveilled by microglia and surrounded by perivascular astrocytes (PVA), which in turn are in contact with synapses. Cerebral ischemia induces the rapid release of the serine proteinase tissue-type plasminogen activator (tPA) from endothelial cells, perivascular astrocytes, microglia and neurons. Owning to its ability to catalyze the conversion of plasminogen into plasmin, in the intravascular space tPA functions as a fibrinolytic enzyme. In contrast, the release of astrocytic, microglial and neuronal tPA have a plethora of effects that not always require the generation of plasmin. In the ischemic brain tPA increases the permeability of the NVU, induces microglial activation, participates in the recycling of glutamate, and has various effects on neuronal survival. These effects are mediated by different receptors, notably subunits of the N-methyl-D-aspartate receptor (NMDAR) and the low-density lipoprotein receptor-related protein-1 (LRP-1). Here we review data on the role of tPA in the NVU under non-ischemic and ischemic conditions, and analyze how this knowledge may lead to the development of potential strategies for the treatment of acute ischemic stroke patients.

Plasminogen activator inhibitor-1 mediates cerebral ischemia-induced astrocytic reactivity.

Although ischemia increases the abundance of plasminogen activator inhibitor-1 (PAI-1), its source and role in the ischemic brain remain unclear. We detected PAI-1-immunoreactive cells with morphological features of reactive astrocytes in the peri-ischemic cortex of mice after an experimentally-induced ischemic lesion, and of a chimpanzee that suffered a naturally-occurring stroke. We found that although the abundance of PAI-1 increases 24 hours after the onset of the ischemic injury in a non-reperfusion murine model of ischemic stroke, at that time-point there is no difference in astrocytic reactivity and the volume of the ischemic lesion between wild-type (Wt) animals and in mice either genetically deficient (PAI-1-/-) or overexpressing PAI-1 (PAI-1Tg). In contrast, 72 hours later astrocytic reactivity and the volume of the ischemic lesion were decreased in PAI-1-/- mice and increased in PAI-1Tg animals. Our immunoblottings and fractal analysis studies show that the abundance of astrocytic PAI-1 rises during the recovery phase from a hypoxic injury, which in turn increases the abundance of glial fibrillary acidic protein (GFAP) and triggers morphological features of reactive astrocytes. These studies indicate that cerebral ischemia-induced release of astrocytic PAI-1 triggers astrocytic reactivity associated with enlargement of the necrotic core.

Lenguaje ictal / Ictal speech

Se presenta el caso de un hombre bilingue (inglés/tailandés) con crisis parciales complejas con articulación de frases ininteligibles en tailandés

Estudio de 300 casos de enfermedad cerebrovascular en al Fundación Santa Fe de Bogotá

Se estudio la historia clínica de 300 pacientes, quienes consultaron a la Fundación Santa Fé de Bogotá entre 1984 y 1988 por enfermedad cerebrovascular. Se hizo diagnóstico de ACV isquémico en 48 por ciento de los casos, de ACV hemorragico en 37 por ciento, de isquemia cerebral transitoria en 15 por ciento y de deficit neurológico en reversión en 1.66 por ciento de los pacientes. El promedio de edad observado para todos los casos fue de 67.33 años con un ligero predominio de pacientes de sexo femenino (52.33 por ciento). Se obervó mortalidad de 6.9 por ciento para el ACV isquemico y de 29 por ciento para el ACV hemorragico. La letalidad en los 300 casos fue de 13.33. La H.T.A. se constituyó como el antecedente más importante para el ACV hemorrágico. Para el ACV isquémico, los antecedentes más importantes fueron tabaquismo, H.T.A. e hipercolesterolemia

Mielinolisis póntica central con síndrome de enclaustramiento

Tha case of a 55 year old man who presented with severe global headache 8 hours after having been drinking heavily, and who over a two hour period developed deep coma and flaccid paralysis of all four extremities is reported. A CT scan of the brain was normal; however, on Magnetic Resonance Imaging (MRI) extensive hyperintense areas in the brain stem, mainly in the pons, were easily identified. Based upon the clinical and MRI findings a diagnosis of Central Pontine Myelinolysis was made. Following several months of supportive therapy the patient partially recovered and was able to leave the hospital.