Substantia nigra lesions in mercaptopropionic acid induced status epilepticus: a light and electron microscopic study

Summary Light microscopic and ultrastructural changes of substantia nigra were studied in paralyzed ventilated rats with status epilepticus induced by mercaptopropionic acid. Some rats were killed at the end of seizure activity and others were examined in varying intervals after the arrest of seizure. The earliest changes were reduction in the size of the neuronal nuclei and chromatin clumping followed by simultaneous distention of axons and dendrites. There was also enlargement of the neuronal perikarya associated with microvacuolation. This neuronal microvacuolation corresponded ultrastructurally to swollen mitochondria with disrupted cristae. These changes were followed by progressive neuronal shrinkage and astrocytic swelling. The swollen astrocytic processes together with swollen neurites gave a spongy appearance to the involved area. The lesion thereafter progressively enlarged and evolved into an area of frank necrosis containing abundant macrophages. This lesion is morphologically different from that produced in cortex and hippocampus by seizure activity or due to the direct effect of excitotoxins. The significance of substantia nigra pars reticularis changes and their pathogenesis are discussed.     

“Marden-Walker Syndrome”: Neuropathologic Findings in Two Siblings

Neuropathologic examination of two siblings with phenotypic features consistent with Marden-Walker syndrome revealed central nervous system abnormalities which include reduction in the number of spinal anterior horn cells. The occurrence of these changes in a sibling pair provides strong evidence for a genetic etiology. The relationship between the neuropathologic changes and other phenotypic manifestations in this syndrome and in the closely related syndrome of Pena-Shokeir are discussed.     

Purkinje cell inclusions and 'atelencephaly' in 13q-chromosomal syndrome

Severe microcephaly was present from birth in a child with a 13q-chromosomal syndrome [46,XY,del(13)(q22q31)]. He died at 20 months of age. Neuropathologic findings included atelencephaly and eosinophilic cytoplasmic inclusions in cerebellar Purkinje cells. Ultrastructurally, the inclusions consisted of stacks of parallel cisternae separated by electron-dense granular material. The relationship between these inclusions and the smaller cytoplasmic inclusions known as "lamellar bodies" is discussed, and the central nervous system malformations in this syndrome are reviewed.     

Treatment and prevention of primary intracerebral hemorrhage

Intracerebral hemorrhage (ICH), which constitutes 10 to 15% of all strokes and affects approximately 65,000 people each year in the United States, has the highest mortality rate of all stroke subtypes. Hypertension, cerebral amyloid angiopathy, and anticoagulation underlie the majority of cases of ICH. Warfarin not only increases the risk but also increases the severity of ICH by causing hematoma expansion. With the advent of gradient-echo magnetic resonance imaging, patients with underlying cerebral amyloid angiopathy or hypertensive vasculopathy can be identified, and measures can be taken to prevent ICH. Initiating an antihypertensive regimen in a patient with nonlobar microbleeds suggestive of hypertensive vasculopathy, and withholding warfarin in patients with lobar microbleeds suggestive of cerebral amyloid angiopathy, are emerging prevention strategies. Although a treatment for cerebral amyloid angiopathy does not exist, agents targeting beta-amyloid metabolism and bioactivity are promising candidates. Strategies for preventing warfarin-associated hemorrhage include strict monitoring of anticoagulation levels and using agents such as direct thrombin inhibitors. The future of ICH management lies in therapies targeted at the pathophysiological steps in ICH. Potential treatments include glutamate receptor antagonists for preventing glutamate excitotoxicity, matrix metalloproteinase and thrombin inhibitors for preventing perihematomal edema, and recombinant activated factor VII for preventing hematomal expansion.     

Neuropathology of seizures in the immature rabbit

Acute morphologic changes of brain due to chemically induced seizures are studied in developing rabbits. Accordingly, rabbits of postnatal days 6 and 7 (p6-7) and p10-12 are injected with a single dose of 1-6 mg/kg kainic acid (KA) intraperitoneally (i.p.) or injected with a single dose of 200-300 mg/kg pilocarpine subcutaneously (s.c.). Many animals developed seizures of varying severity and length. Histologic examination of brain 2 days following injection showed that KA-induced seizures did not cause neuronal death. Pilocarpine-induced seizures resulted in neuronal death mainly involving the CA1 region of hippocampus. In the p6-7 group, only a small number of brains were involved, lesions were mild and limited to CA1. In the p10-12 group, majority of the brains were damaged, lesions were relatively severe, and in some brains extended beyond the CA1 region involving the subiculum, CA3, cortex, and amygdala. Measurements of physiologic parameters indicate that these changes were not secondary to hypoxemia during seizures. However, there was hypotension and hyperthermia, both of which may contribute to brain damage during seizures. The findings suggest that pilocarpine-induced seizures during the second postnatal week in rabbits is a useful model to study the morphologic changes of brain due to seizure in the developing animal and also to assess the systemic physiologic alterations during seizures.     

Effect of differentiation inducers on growth characteristics of human glioma cell lines

Summary The effect of dimethylsulfoxide (DMSO) and iododeoxyuridine (IUdR) on the growth characteristics of two established human glioblastoma cell lines (FG and HMCN-1) was studied. The FG cell line has been characterized. The HMCN-1 cell line, established in our laboratory, consisted of fibroblastoid and polygonal cells that grew without contact inhibition. Subcutaneous injection of these cells into weanling athymic nude mice induced slowly growing, solid tumors that were histologically spindly with areas that were similar to the original tumor. Chromosomal analyses revealed a human heteroploid pattern with a modal number of 69. The cells of the original human glioma contained S-100 protein and glial fibrillary acidic protein (GFA protein), whereas the established cells failed to express markers. Prolonged treatment of glioma cells with DMSO generated a more adherent, normal human fibroblastoid phenotype that grew with contact inhibition. The new phenotype and proliferative restriction of these cells was evident as late as 50 days after discontinuation of treatment. The chemical induction of cell differentiation resulted in decreased tumorigenic potential in athymic nude mice.     

Five children with del (2)(q31q33) and one individual with dup (2)(q31q33) from a single family: review of brain, cardiac, and limb malformations

Five matings to a dir ins (6;2)(q16;q31q33) carrier have produced a high frequency (42%) of offspring with unbalanced karyotypes. Five children have the derivative chromosome 2 resulting in del (2)(q31q33) and one individual received the derivative chromosome 6 leading to dup (2)(q31q33). The findings associated with the deletion include pre- and postnatal growth retardation, developmental delay, minor facial anomalies, seizures, complex structural heart defects, and limb deficiency. Autopsy of one individual showed complex brain malformations including hydrocephalus secondary to obstruction of the foramina of Monro, extensive heterotopias and polymicrogyria, and an unusual form of total anomalous pulmonary venous return. We compare the findings in these children to those of previously reported cases and construct an overview of the range of anomalies. Apparently, no other individual with dup (2)(q31q33) has been described. We compare the physical peculiarities of our patient with those of individuals with duplications of overlapping regions of 2q.