Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0264733 (ventricular dilatation)
 2,163 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brain reperfusion may be of particular importance in the etiology of periventricular leukomalacia, of which the common findings are gliosis and ventricular dilatation. To investigate the mechanism of this pathogenesis, we used a metabolic inhibition (MI) model using cyanide plus deoxyglucose treatment of cultured glia isolated from fetal rat brain and examined the activity of extracellular signal-regulated protein kinase (ERK) during MI and also during the recovery from MI of 30 min. ERK activation was stimulated during MI and the recovery from MI. The time course and extent of activation of ERK during MI and the recovery from MI, however, were distinctly different. Activation of ERK was stimulated within 5 min of MI and declined thereafter. Activation of ERK was sustained during the recovery phase from MI and the extent of the activation was much greater than that during MI. Pretreatment with EGTA to eliminate extracellular Ca(2+), or with APV, an NMDA receptor antagonist, to inhibit Ca(2+) influx through the NMDA receptor, attenuated the activation of ERK. Moreover, pretreatment with PMA to downregulate PKC abolished the activation of ERK. PD98059, an inhibitor of ERK kinase, attenuated the cell proliferation induced by MI followed by recovery from MI. These results suggest that ERK is involved in gliosis during the recovery phase from MI and may play a role in the etiology of periventricular leukomalacia.
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PMID:Involvement of extracellular signal-regulated protein kinase in gliosis induced during recovery from metabolic inhibition. 1067 87

PKN (protein kinase N; also called protein kinase C-related kinase (PRK-1)), is a serine/threonine protein kinase that is ubiquitously expressed in several organs, including the brain. PKN has a molecular mass of 120 kDa and has two domains, a regulatory and a catalytic domain, in its amino-terminals and carboxyl-terminus, respectively. Although the role of PKN has not been fully elucidated, previous studies have revealed that PKN is cleaved to a constitutively active catalytic fragment of 55 kDa in response to apoptotic signals. Hydrocephalus is a pathological condition caused by insufficient cerebrospinal fluid (CSF) circulation and subsequent excess of CSF in the brain. In this study, in order to elucidate the role of PKN in the pathophysiology of hydrocephalus, we examined PKN fragmentation in hydrocephalic model rats. Hydrocephalus was induced in rats by injecting kaolin into the cisterna magna. Kaolin-induced rats (n=60) were divided into three groups according to the observation period after treatment (group 1: 3-6 weeks, group 2: 7-12 weeks, and group 3: 13-18 weeks). Sham-treated control rats, injected with sterile saline (n=20), were similarly divided into three groups. Spatial learning ability was estimated by a modified water maze test. Thereafter, brains were cut into slices and ventricular dilatation was estimated. Fragmentation of PKN was observed by Western blotting in samples collected from the parietal cortex, striatum, septal nucleus, hippocampus, and periaqueductal gray matter. All kaolin-induced rats showed ventricular dilatation. Most of them showed less spatial learning ability than those of sham-treated controls. In most regions, fragmentation of PKN had occurred in a biphasic manner more frequently than that in controls. The appearance of PKN fragmentation in periaqueductal gray matter was correlated with the extent of ventricular dilation and spatial learning disability. These results revealed that PKN fragmentation was observed in rats with kaolin-induced hydrocephalus, models for chronically-damaged brain dysfunction, suggesting that persistent brain insult, such as apoptosis, had occurred in these models. PKN fragmentation could be a hallmark for evaluating morphological and functional damage of the hydrocephalus.
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PMID:Fragmentation of protein kinase N (PKN) in the hydrocephalic rat brain. 1789 75