Alteration of gap junction proteins (connexins) following lateral fluid percussion injury in rats.

Gap junctions are intercellular channels that mediate the cytoplasmic exchange of small hydrophilic molecules and are formed by a family of integral membrane proteins called connexins (Cxs). Cx43 is expressed predominantly in astrocytes, while Cx36 is expressed in neurons. In this study, we show alteration of Cx43 and Cx36 in the hippocampus after traumatic brain injury in rats. Adult male Sprague-Dawley rats were subjected to lateral fluid percussion injury of moderate severity. Brain coronal sections were used for immunohistochemistry with Cx43 and Cx36 antibodies. Cx43 immunoreactivity was increased in reactive astrocytes in the damaged hippocampus 24 hours after injury, and persisted for 72 hours. On the other hand, Cx36 immunoreactivity increased in CA3 neurons 1 hour after injury, and decreased later. These results indicate that gap junctions might participate in the pathophysiological process after traumatic brain injury.

Optic nerve hyperintensity on T2-weighted images among patients with pituitary macroadenoma: correlation with visual impairment.

PURPOSE: Visual acuity (VA) disturbance other than field defect is important in evaluating patients with pituitary macroadenoma. The purpose of this study was to evaluate MR imaging appearances of optic nerves in patients with pituitary macroadenoma and to ascertain whether visual impairment was correlated with abnormality in optic nerve signal intensity. PATIENTS AND METHODS: Twenty-seven patients with pituitary macroadenoma were examined. Optic nerves were evaluated on T2-weighted images and correlations of signal intensity abnormality with VA disturbance, visual field disturbance, degree of optic chiasm compression, pathologic findings of surgical specimen, and disease duration were statistically analyzed. Correlations between recovery of VA after treatment and the above-mentioned factors were also determined. RESULTS: Coronal T2-weighted images demonstrated unilateral optic nerve hyperintensity lesions in 9 patients. Bilateral signal intensity abnormality of the optic nerve was seen in 5 patients. Signal intensity abnormality of the optic nerve was seen at the site of compression and in the ventral side of the tumor. These patients did not demonstrate signal intensity abnormality posterior to the tumor. Presence of such signal intensity abnormalities was correlated with the degree of optic chiasmal compression and with VA disturbance. Recovery of VA after treatment was correlated with disease duration. CONCLUSION: Hyperintensity of the optic nerves ventral to the pituitary macroadenoma was associated with VA impairment. Recovery of VA after treatment was correlated with disease duration. MR imaging of the optic nerves can provide valuable information for management of pituitary macroadenoma.

A role of glial fibrillary acidic protein in hippocampal degeneration after cerebral trauma or kainate-induced seizure.

Astrocytes perform a variety of functions in the adult central nervous system (CNS). Recent evidence suggests the robust upregulation of glial fibrillary acidic protein (GFAP) after CNS insult. However, little is known about the role of GFAP in the hippocampal degeneration after brain injury. We herein compared the GFAP knockout (KO) and wild type (WT) mice on the histological and behavioral outcome in response to cerebral trauma or kainic acid (KA)-induced seizure. Although all KO mice showed hippocampal CA3 neuronal degeneration. WT mice did not show any neuronal degeneration in CA3 subfield at 72 hrs after trauma. Thereafter, KO mice showed a higher susceptibility to KA-induced seizures and an increased number of pyknotic CA3 neurons 72 hrs after KA administration. These results indicate that GFAP plays a crucial role in the hippocampal neurodegeneration after CNS insult.

Mitogen-activated protein kinases phosphorylation in posttraumatic selective vulnerability in rats.

Mitogenic stimulation of the Mitogen-activated protein kinase (MAPK) pathway modulates the activity of many transcriptional factors leading to biological responses. Of these, three MAPK cascades are well characterized as extracellular signal-regulated protein kinase (ERK), c-Jun NH(2)-terminal kinase (JNK), and p38 pathways. The aim of this study was to investigate the topographic distribution and the role of activated MAPK pathways after fluid percussion injury (FPI) in rats. In the present results, FPI significantly induced ERK- and JNK-phosphorylation, but not p38-phosphorylation in the cortex and hippocampus at the injury site. The immunoreactivity for phospho-ERK was localized in the superficial neuronal layers, dentate hilar neurons, and the damaged CA3 neurons after 30 mins of FPI. Double immunostaining showed that phospho-ERK was prominent in astrocytes 6 hrs after TBI. The current results suggest that MAPK pathways are involved in signal transduction after FPI.

Focal brain edema and natriuretic peptides in patients with subarachnoid hemorrhage.

Central salt wasting syndrome may be caused by pathological increases in serum natriuretic peptides after subarachnoid hemorrhage (SAH). However, it is unclear as to why the serum concentration of atrial natriuretic peptide (ANP) or brain natriuretic peptide (BNP) increases in the subacute phase of SAH. The present study was designed to assess the correlation between focal brain edema and serum concentration of ANP or BNP in patients with SAH. Focal brain edema was found in 8 SAH-patients and peaked between days 4 and 7 of SAH. The mean serum ANP and BNP levels in patients with focal brain edema were significantly higher than those in patients without focal brain edema between days 4 and 14 of SAH. These results suggest that focal brain edema might correlate with increased levels of ANP and BNP in the subacute phase of SAH.

Vascular endothelial growth factor expression in pituitary adenomas.

Vascular endothelial growth factor (VEGF) is known to be a mediator of angiogenesis and vascular permeability. A cystic component and hemorrhage are often found in pituitary adenomas. In the present study we assess the VEGF expression based on immunohistochemical examinations in 48 pituitary adenomas. All the adenomas showed some VEGF immunoreactivity mainly in the cytoplasm of tumor cells. Of the 48 adenoma-cases, 16 cases had a strong VEGF immunoreactivity, 26 cases had a moderate one, and 6 cases had a weak one. On the MR images, a cystic component was found in 16 cases (33.3%), and a hemorrhage was found in 18 cases (37.5%). The VEGF immunoreactivity had a significant relationship with the cystic component but neither the hemorrhage, size, recurrence, or HE classification. These findings suggest that VEGF might play a potential role in the pathogenesis of cystic formation in pituitary adenomas.

MRI analysis of hydrocephalus associated with acoustic neurinoma.

We investigated the hydrocephalus in 24 patients associated with acoustic neurinoma. We found the high incidence of homo-lateral ventricular dilatation to the side of the acoustic neurinoma. Utilizing magnetic resonance imaging, the diameter of the tumor parallel to the pyramidal bone, diameter of the tumor perpendicular to the pyramidal bone, grade of the 4th ventricle deviation, and the shape of the tumor (round or oval) were analyzed. Ten (42%) of the 24 patients with acoustic neurinoma were found to have hydrocephalus. Seven (70%) of the 10 patients with hydrocephalus exhibited asymmetrical lateral ventricle dilatation: in all cases the lateral ventricle in the hemisphere homolateral to the acoustic neurinoma was larger than that of the contralateral side. The hydrocephalus was not related to the grade of the 4th ventricle deviation but rather to the diameter of the tumor parallel to the pyramidal bone (p < 0.01). The diameter of the tumor parallel to the pyramidal bone was also related to the asymmetrical lateral ventricular dilatation (p < 0.05).

Characteristic phosphorylation of the extracellular signal-regulated kinase pathway after kainate-induced seizures in the rat hippocampus.

Extracellular signal-regulated kinase (ERK) pathways play a crucial role in cell growth and long-lasting neuronal plasticity. Several studies have shown that phosphorylated-ERK (p-ERK) significantly increases after kainic acid (KA) administration. However, little or no information is available about the spatial distribution of p-ERK after KA-induced seizures. We herein show that KA-induced seizures significantly increase p-ERK in both neurons and astrocytes in rat brain using Western blots and immunohistochemistry. A strong immunoreactivity for p-ERK was induced in the dentate hilar neurons and CA3 neurons 30 mins and 6 hrs after KA injection. In addition, immunoreactivity for p-ERK was seen in astrocytes 6 hrs after KA injection. 72 hrs after KA injection, all pyramidal neurons had died. These findings suggest that the ERK pathway participates in the KA-induced neurotoxicity in the rat hippocampus.

Extracellular superoxide dismutase following cerebral ischemia in mice.

We describe the changes in extracellular superoxide dismutase (EC-SOD) following cerebral ischemia in mice. Mice were subjected to transient forebrain ischemia and reperfusion. The measurements of EC-SOD using ELISA showed increased brain EC-SOD after 24 h of reperfusion. The immunohistochemical examination showed that EC-SOD immunoreactivity in cortical and striatal capillary wall was conspicuous after 3 h. EC-SOD immunoreactivity was also noted in cortical neurons after 24 h. Northern blot analysis showed an increased EC-SOD mRNA expression in the brain after 24 h. In situ hybridization study demonstrated no mRNA expression of EC-SOD following ischemia and reperfusion in the capillary wall. These findings suggest that serum EC-SOD might accumulate on brain endothelial cells, while cortical neurons produce EC-SOD themselves after cerebral ischemia with reperfusion.

ICP monitoring following bilateral carotid occlusion in GFAP-null mice.

To investigate the possible role of glial fibrillary acidic protein (GFAP) in cerebral ischemia, we have monitored the intracranial pressure (ICP) and local cerebral blood flow (ICBF) following bilateral carotid artery occlusion (BCAO) in GFAP-null mice and their wild type littermates. GFAP-null mice (B6, 129-GfaptmlMes) were obtained from Jackson Laboratories. The ICP and ICBF was continuously monitored during 15 minutes BCAO and reperfusion. The variation of the circle of Willis was also investigated in both GFAP-null and wild type mice. The breakdown of blood brain barrier (BBB) was assessed by immunohistochemical staining against mouse immunogloblins (IgG). A significantly more profound and immediate decrease in ICBF after BCAO was observed in GFAP-null mice (p < 0.04, ANOVA). GFAP-null mice also showed a significant increase (% change) in ICP after reperfusion (p < 0.05, ANOVA). There were no gross differences in the circle of Willis between GFAP-null and wild type mice. No abnormal IgG immuno-reactivity was observed in the forebrain of both animals. These results indicate a high susceptibility to cerebral ischemia in GFAP-null mice and suggest an important role for astrocytes and GFAP in the progress of ischemic brain damage and increased ICP after cerebral ischemia with reperfusion.

Female gender as a risk factor for hypokalemia and QT prolongation after subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) often causes hypokalemia and QT prolongation. The sex disparities among 73 patients with SAH and 96 control subjects were examined. On the first day of SAH, the mean serum potassium level was significantly lower and the mean corrected QT interval was significantly longer in the female SAH group compared with either the female control or male SAH group. These findings suggest female susceptibility to hypokalemia and QT prolongation after SAH.

Primary central nervous system lymphoma with paraproteinemia.

BACKGROUND: Although 34% to 54% of cases of extraneural non-Hodgkin's lymphoma (NHL) of the B-cell type are associated with monoclonal paraproteinemia, primary central nervous system NHL (PCNSL) with paraproteinemia has rarely been reported. The authors present herein a case of PCNSL with monoclonal immunoglobulin M (IgM) paraproteinemia. METHODS AND RESULTS: A 78-year-old woman was referred to our hospital because of hemiparesis and epilepsy. Magnetic resonance imaging showed a round mass in the left frontal region. Serum IgM was 3,820 mg/dL, and immunofixation revealed an IgM kappa monoclonal paraprotein. No lymphoplasmacytic infiltration was observed on bone marrow aspiration. The brain tumor was totally resected. The pathological diagnosis was NHL (diffuse, large B cell). The results of immunohistochemical staining for IgM were strongly positive in the tumor cells. CONCLUSION: This type of PCNSL has rarely been reported and little is known about it. It is possible that the true incidence of paraproteinemia caused by PCNSL is higher than has been thought. The clinical features of the tumor and pertinent literature are reviewed.

Peduncular hallucinosis due to a pineal meningioma. Case report.

The authors report the case of a 53-year-old woman who experienced visual hallucinations diagnosed as peduncular hallucinosis (PH). The cause of the PH was compression of the quadrigeminal plate and/or the splenium due to a meningioma originating from the falcotentorial junction (pineal meningioma). The nature of the visual hallucinations was depicted in drawings created by the patient herself. This is the first report of PH caused by a tumor located in the pineal region.

Evaluation of spontaneous intracranial hypotension: assessment on ICP monitoring and radiological imaging.

We describe two recent cases of spontaneous intracranial hypotension. A 38-year-old woman developed a severe postural headache. Magnetic resonance imaging (MRI) showed marked dural enhancement. Histopathological findings of dural biopsy showed numerous dilated vessels in the dura, rather than hypertrophic change. Lumber CSF pressure was 5 cmH2O and RI cisternography suggested CSF leakage. A 58-year-old woman with postural headache and vertigo had bilateral subdural haematoma associated with diffuse dural enhancement on MRI. Lumber CSF monitoring confirmed persistent low pressure ranging from 0-5 cm H2O. MRI myelography revealed multiple CSF pouches along the whole spinal axis. CSF leakage was demonstrated on Radioisotope (RI) cisternography. Both cases described in this report were diagnosed as spontaneous intracranial hypotension caused by CSF leakage from spinal meningeal diverticula and were successfully treated by intravenous Factor XIII administration.

Preferential conditions for and possible mechanisms of induction of ischemic tolerance by repeated hyperbaric oxygenation in gerbil hippocampus.

OBJECTIVE: We reported previously that repeated hyperbaric oxygenation (HBO) as pretreatment induced ischemic tolerance in the gerbil hippocampus. This study was conducted to determine the preferential conditions for induction of ischemic tolerance by HBO and the mechanism of this induction through immunohistochemical analysis of Bcl-2, Bax, and manganese superoxide dismutase expression. METHODS: Five-minute forebrain ischemia was produced in gerbils after pretreatment with 2 atmospheres absolute (ATA) HBO once every other day for one, three, or five sessions, 2 ATA hyperbaric air once every other day for five sessions, or 3 ATA HBO once daily for 10 sessions. Histological examinations were then performed. Two days after pretreatment with 2 ATA HBO once every other day for five sessions or with 3 ATA HBO once daily for 10 sessions, sections were analyzed immunohistochemically. RESULTS: Pretreatment with 2 ATA HBO once every other day for three or five sessions induced ischemic tolerance; however, pretreatment with 2 ATA HBO for one session, 2 ATA hyperbaric air once every other day for five sessions, or 3 ATA HBO once daily for 10 sessions did not. Pretreatment with 2 ATA HBO once every other day for five sessions, but not with 3 ATA HBO once daily for 10 sessions, significantly increased Bcl-2 and manganese superoxide dismutase immunoreactivity in the CA1 sector. CONCLUSION: These results suggest that protection against mitochondrial alterations after ischemia through manganese superoxide dismutase and/or Bcl-2 expression may be related to induction of ischemic tolerance by repeated HBO pretreatment.

[Influence of intubation maneuver with or without premedication for intracranial hemorrhage with unconsciousness].

PURPOSE: To clarify the influence of intubation maneuver with or without premedication for intracranial hemorrhage with unconsciousness. METHODS: Between May 1995 and May 2000, we analyzed retrospectively 46 patients who had received intubation for unconsciousness and were found non-traumatic intracranial hemorrhage by head computer tomography at the Trauma and Critical Care Center, National Defense Medical College. They were divided into two groups, Drug group in which drugs were used before intubation and Control group which were intubated without drugs. Physical findings on admission, head CT findings, Glasgow Outcome Score(GOS) at discharge were analyzed between the groups. RESULTS: There were no significant differences for background of subjects between the groups. In the Drug group, diazepam, pentazocine, lidocaine, nifedipine and nicardipine were used before intubation. GOS in the Control group was significantly greater than in the Drug group(p < 0.01). CONCLUSION: In case of intubation for unconscious patients who may suffer intracranial hemorrhage, using premedication leads to favorable outcome.