The authors review the pertinent literature dealing with all aspects of cerebral cavernous malformations in the adult. Clinical, neuroradiological, pathological, and epidemiological aspects are presented. The clinical significance of bleeding from cavernous malformations and various hemorrhage patterns are discussed in relation to the factors that influence hemorrhage rates. Recent reports describing the genetic mechanisms of inheritance, de novo formation, and angiogenesis of cavernomas are reviewed as well. Brainstem cavernomas have received special attention, since their clinical management is controversial in the literature. Presently, microsurgical removal is favored by the majority of authors and stereotactic radiosurgery appears to be inappropriate for prevention of bleeding from a cavernoma. Our own case material consists of data of 72 patients operated upon during the past 5 years. Twenty-four patients harbored the lesion within the brainstem, 18 within the deep white matter of the hemispheres, 12 in the basal ganglia or thalamus, 11 in superficial areas of the hemisphere, and seven within the cerebellum. The perioperative morbidity rate was 29.2% (21/72) while the rate of long-term morbidity was 5.5% (4/72), with no mortality in this series. It is concluded that cerebral cavernous malformations, including lesions in critical regions of the brain, can be treated microsurgically with excellent results and an acceptable morbidity.

Summary: Transient arrest of the cerebral blood circula tion results in neuronal cell death in selectively vulnera ble regions of the rat brain. To elucidate further the in volvement of glial cells in this pathology, we have studied the temporal and spatial distribution pattern of activated microglial cells in several regions of the ischemic rat brain. Transient global ischemia was produced in rats by 30 min of a four-vessel occlusion. Survival times were 1, 3, and 7 days after the ischemic injury. The microglial reaction was studied immunocytochemically using sev eral monoclonal antibodies, e.g., against CR3 comple ment receptor and major histocompatibility complex (MHC) antigens. Two recently produced monoclonal an tibodies against rat microglial cells, designated MUC 101 and 102, were also used to identify microglial cells. Fol lowing ischemia, the microglial reaction was correlated Transient arrest of the cerebral blood circulation leads to neuronal damage in selectively vulnerable regions of the CNS. Pyramidal neurons of the CAl area in the hippocampus, neocortical neurons in the layers III, V, and VI, as well as neurons in the dorsolateral striatum are most vulnerable to tran sient ischemia (Spielmeyer, 1925;Scholz, 1953;Brown and Brierley, 1972; Pulsinelli et aI., 1982a,b; Schmidt-Kastner and Rossmann, 1988;Schmidt Kastner and Freund, 1991). In contrast, there are other neurons, e.g., CA3 pyramidal cells, that are comparatively resistant to transient ischemia (Schmidt-Kastner and Rossmann, 1988). The criti-

Hepatocyte growth factor (HGF), a natural ligand for the c-met protooncogene product, exhibits mitogenic, motogenic, and morphogenic activities for regeneration of the liver, kidney, and lung. Recently, HGF was clearly shown to enhance neurite outgrowth in vitro. To determine whether HGF has a neuroprotective action against the death of neurons in vivo, we studied the effect of HGF on delayed neuronal death in the hippocampus after 5-minute transient forebrain ischemia in Mongolian gerbils. Continuous postischemic intrastriatal administration of human recombinant HGF (10 or 30 micrograms) for 7 days potently prevented the delayed death of hippocampal neurons under both anesthetized and awake conditions. Even when HGF infusion started 6 hours after ischemia (i.e., in a delayed manner), HGF exhibited a neuroprotective action. We conclude that HGF, a novel neurotrophic factor, has a profound neuroprotective effect against postischemic delayed neuronal death in the hippocampus, which may have implications for the development of new therapeutic strategies for ischemic neuronal damage in humans.

Mitogen-activated protein kinases, which play a crucial role in signal transduction, are activated by phosphorylation in response to a variety of mitogenic signals. In the present study, the authors used Western blot analysis and immunohistochemistry to show that phosphorylated extracellular signal-regulated protein kinase (p-ERK) and c-Jun NH2-terminal kinase (p-JNK), but not p38 mitogen-activated protein kinase, significantly increased in both the neurons and astrocytes after traumatic brain injury in the rat hippocampus. Different immunoreactivities of p-ERK and p-JNK were observed in the pyramidal cell layers and dentate hilar cells immediately after traumatic brain injury. Immunoreactivity for p-JNK was uniformly induced but was only transiently induced throughout all pyramidal cell layers. However, strong immunoreactivity for p-ERK was observed in the dentate hilar cells and the damaged CA3 neurons, along with the appearance of pyknotic morphologic changes. In addition, immunoreactivity for p-ERK was seen in astrocytes surrounding dentate and CA3 pyramidal neurons 6 hours after traumatic brain injury. These findings suggest that ERK and JNK but not p38 cascades may be closely involved in signal transduction in the rat hippocampus after traumatic brain injury.

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