The nature of SVD appears to have been modified by effective treatment of hypertension. Classic risk factors are often absent. The hypothesis that a variety of conditions that enhance small-vessel permeability may contribute to the pathogenesis of SVD merits consideration.

The aetiopathogenesis of small, deep (lacunar) infarcts remains controversial. The view that they are caused by occlusive intrinsic small vessel disease is widely held, but is based on only a small number of detailed pathology studies. We describe and illustrate a variant of small, microvessel-associated basal ganglia lesion, the histopathological features of which are distinct from those of classical Types I, II and III lacunes. Their appearances suggest a state of incomplete infarction. The pathogenetic significance of such lesions is discussed, in particular the role of mechanisms causing temporary or only moderately severe ischaemia.

Reactive astrocytosis is a well-documented feature of HIV encephalitis (HIVE), but it is unclear whether restricted infection of astrocytes contributes to this phenomenon. In addition, the part played by reactive and/or infected astrocytes in AIDS-related dementia is not fully understood. In this study of patients at different stages of the human immunodeficiency virus (HIV) infection, who had been treated at most with one antiretroviral drug, reactive astrocytes were identified by immunopositivity for glial fibrillary acidic protein (GFAP) and infected astrocytes by positivity for HIV Nef protein. Results were compared for drug-using AIDS patients with (n=9) and without (n=7) HIVE, for presymptomatic HIV-positive drug users (n=12) and for control HIV-negative subjects (n=20), including a group who used drugs (n=10). GFAP-reactive astrocytes in both grey and white matter were significantly more numerous in HIVE subjects than in each of the other groups but did not correlate with viral load. Nef-positive astrocytes were confined to HIVE cases and to white matter, but were numerous in only one subject who was treatment-naive. Nef-positive microglia were identified in all HIVE cases and in occasional AIDS and presymptomatic subjects who did not have HIVE. The results suggest that astrocytes may form an additional viral reservoir in late HIV infection and may contribute to HIVE. However, the number of GFAP-positive astrocytes was neither increased in pre-AIDS nor in drug abuse, in contrast with microglia which we have shown previously to be up-regulated in both states.

We have characterized the early brain pathology in Sprague-Dawley rats subjected to a modified Richmond impact acceleration model of closed head injury (CHI). This model was modified to produce maximal traumatic brain injury (TBI) in the absence of skull fracture, extracerebral or intracerebral hemorrhage, or brain contusion. We then used this model to assess the neuropathologic effects of superimposed secondary insults, which were designed to reflect a clinically relevant combination of hypotension and pyrexia. Acute neuronal injury, blood-brain barrier (BBB) integrity, axonal injury (AI), and glial activation were studied 4 1/2 hours following either CHI (group A), CHI plus secondary insults (group B), secondary insults alone (group C), or sham control injury (group D). There was evidence of limited AI following CHI in the lower medulla and upper cervical cord region, which was not modified by addition of secondary insult. Loss of dendritic microtubule-associated protein MAP2 immunoreactivity proved a reliable marker of acute neuronal damage, which was confined to subimpact and inferolateral cortical locations following CHI and was widespread after secondary insult. The pattern of plasma protein extravasation paralleled that of acute neuronal injury. We found no evidence of microglial activation, either local or generalized, by 4 1/2 hours. However, by this time CHI and secondary insults had combined to produce evidence of subimpact astrocyte activation, which was not apparent with either insult or injury alone. We conclude that in this modified Richmond model of CHI, when combined with secondary insults, there is no convincing potentiation of brain damage with the minor exception of astrocyte activation.