Cerebral Hypoperfusion and Delayed Hippocampal Response After Induction of Adult Kaolin Hydrocephalus

Abstract

Background and Purpose-In chronic hydrocephalus, a role for tissue hypoxia resulting from cerebrovascular compression is suggested. The purpose of this study was to evaluate whether changes in cerebral blood flow (CBF) in the time course of adult kaolin-induced hydrocephalus correlated with immunohistochemical neuronal responses. Methods-In 46 adult Sprague-Dawley rats, kaolin hydrocephalus was induced and immunostaining of neurofilament protein (NF68), synaptophysin (SYN38), and neuronal nitric oxide synthase (NOS) was performed at 2 (short term), 4 (intermediate term), and 6 and 8 (long term) weeks. Local CBF was measured quantitatively by [ 14 C]iodoantipyrine ([ 14 C]IAP) autoradiography in the short-term stage and in both long-term stages. Results-At 2 weeks, neuronal NOS immunoreactivity was globally increased in cortical areas and within the hippocampus. Four weeks after hydrocephalus induction, a reactive increase of SYN38 and NF68 immunoreactivity in the periventricular cortex was seen. At 6 and 8 weeks, when the ventricular size was decreasing, immunohistochemical changes in the hippocampus became most evident. A maintained toxic NOS reactivity in the CA1 subfield was accompanied by a loss of NF68 staining. In the CA3 subfield, however, focal increases in NF68 and SYN38 immunoreactivity were found. Cortical and hippocampal blood flow showed prolonged decreases of 25% to 55% compared with control animals. At 8 weeks, control levels were reached. Conclusions-The observed temporary CBF decrease appears to correlate with an early global neuronal ischemic response.In addition, it may also account for the delayed selective response of ischemia-vulnerable structures, eg, hippocampus, in chronic adult kaolin-induced hydrocephalus.

Neuroprotective effect of memantine on hippocampal neurons in infantile rat hydrocephalus

“…In their study, Klinge et al reported a global increase in NOS immunoreactivity in hippocampal neurons in kaolin-induced hydrocephalic adult rats two weeks after the induction. This increase was demonstrated to be in correlation with decreasing of cerebral blood flow at the early stage of hydrocephalus (16). They postulated that the global increase in hippocampal NOS staining of hydrocephalic subjects appeared to indicate a toxic neuronal response (16).…”

“…There are few studies comprehensively describing the injury mechanism in hippocampus during hydrocephalus (6,8,16,17,25). It has been observed that as long as the hydrocephalic process progresses, consequent alterations emerge preferably at those areas sensitive to ischemia.…”

“…This increase was demonstrated to be in correlation with decreasing of cerebral blood flow at the early stage of hydrocephalus (16). They postulated that the global increase in hippocampal NOS staining of hydrocephalic subjects appeared to indicate a toxic neuronal response (16). Considering the important role of neuronal NOS enzyme in the acute excitotoxic injury of the central nervous system, an excitotoxic injury could be mentioned in the hydrocephalic process at hippocampus.…”

“…It has been observed that as long as the hydrocephalic process progresses, consequent alterations emerge preferably at those areas sensitive to ischemia. There are few studies comprehensively describing the injury mechanism in hippocampus during adult hydrocephalus (6,8,16,25). Published data indicating the negative impacts of the hydrocephalic process on the hippocampus of the immature brain are even fewer in number (17).…”

Quantification of cerebrospinal fluid transport across the cribriform plate into lymphatics in rats

“…Apart from cost considerations, CSF dynamics in rats have been studied extensively (9,12,15,22,29), and a strong connection between CSF and extracranial lymph has already been made in this species (4,19,23,26,40). Additionally, the rat has proven to be an important species for the study of CSF disorders such as hydrocephalus (1,10,20,21,24,27,31,34,39). Nonetheless, many of the experimental protocols designed for use in sheep are difficult to apply to rats because of the relatively small size of the latter.…”