Cerebral blood flow and glucose metabolism of the ischemic rim in spontaneously hypertensive stroke-prone rats with occlusion of the middle cerebral artery.

To determine acute postischemic metabolic changes of the ischemic rim under conditions of poor collateral circulation, we examined cerebral blood flow and glucose metabolism in the area of the brain around the ischemic tissue in 36 male spontaneously hypertensive stroke-prone rats (SHRSP) in the acute stage of focal ischemia. The right middle cerebral artery (MCA) was occluded dorsal to the rhinal fissure. Four hours after occlusion, local cerebral blood flow (LCBF), glucose content (LCGC), and glucose utilization (LCGU) were measured by quantitative autoradiographic techniques. The lumped constant was determined from the corresponding LCGC. LCBF showed a widespread and marked decrease in the cortex surrounding the ischemic core, in the thalamus, and in the medial portion of the striatum in the MCA-occluded hemisphere, while the lateral segment of the striatum showed an increase of 36%, compared with findings on the contralateral side. LCGC showed little regional variation, but there was an increase of 38% in the zone bordering the ischemic area. LCGU at the cortex surrounding the ischemic core and in the external capsule showed an increase of 55%. The cortex surrounding the ischemic core, the thalamus, and the lateral segment of the striatum in the MCA-occluded hemisphere showed significant decreases in LCGU. It has been speculated that a high accumulation of glucose reflects a demand for glucose for anaerobic glycolysis in the border areas and that such a demand is probably greater in cases of impaired oxygen delivery due to the presence of microcirculatory disturbances in the MCA-occluded SHRSP.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium accumulation following middle cerebral artery occlusion in stroke-prone spontaneously hypertensive rats.

Delayed neuronal damage in the ischemic region of the rat brain following middle cerebral artery (MCA) occlusion in stroke-prone spontaneously hypertensive rats was studied. The distribution of neuronal damage was determined by 45Ca autoradiography. Accumulation of 45Ca was observed in the corpus callosum and ipsilateral cerebral cortex immediately following MCA occlusion. After 3 days of occlusion, 45Ca had accumulated in the ipsilateral pyramidal tract, the ventral posterior nucleus of the thalamus, and the lateral portion of the striatum. Significant accumulation of 45Ca was observed in the same areas after 7 and 14 days of occlusion. Next the effect of MK-801 on accumulation of 45Ca after MCA occlusion was examined using the same technique. MK-801 (0.5-10 mg/kg i.v.) or saline was administered 15 min before MCA occlusion, and volumes of accumulation of 45Ca were calculated 1 week after ischemic insults. MK-801 significantly reduced 45Ca uptake in the cortex, striatum, and thalamus. Furthermore, there was a strong statistical correlation between the volume of accumulation of 45Ca in the cortex and that in the thalamus (r = 0.8974; p < 0.001; n = 25). We speculate that delayed neuronal damage in the corpus callosum, ipsilateral pyramidal tract, and thalamus may be caused by secondary neuronal degeneration. However, neuronal damage in the striatum, a segment not supplied by the MCA, may be related to excessive release of glutamate.

Immediate cerebrovascular responses to closed head injury in the rat.

Changes in cerebrovascular dynamics were investigated immediately after closed head injury in the rat using a newly developed closed head injury model developed by Marmarou et al. Intracranial pressure (ICP) and mean arterial blood pressure (MABP) were monitored before and after trauma. Regional cerebral blood flow (rCBF), regional cerebral plasma volume (rCPV), and blood-brain barrier (BBB) permeability were measured autoradiographically with iodo[14C]antipyrine [14C]sucrose, and [alpha-14C]aminoisobutyric acid, respectively. rCBF responses to induced hypertension after trauma were measured by laser-Doppler flowmetry to investigate the status of autoregulation. Before injury, baseline ICP values ranged from 6 to 10 mm Hg in all animals. Immediately after trauma, ICP increased synchronously with MABP to > 100 mm Hg and then rapidly returned to baseline values: MABP increased rapidly by 20% after trauma and returned to baseline values within 30 sec. At 30 sec after injury, a significant increase in rCBF was observed in five subcortical regions (p < 0.05), and a significant increase in rCPV was observed in the frontal cortex, parietal cortex, thalamus, and hypothalamus (p < 0.05). At 10 min after injury, BBB permeability (the transfer constant for [alpha 14C]aminoisobutyric acid) was < 0.1 mL/kg/min for all regions except those with a relatively permeable BBB, for example, median eminence, choroidal plexus, pineal body, and pituitary gland. Induced hypertension resulted in a prolonged increase in rCBF after trauma. Thus, in this closed head injury model, which is not associated with marked hypertension or prolonged BBB disruption, widespread increases in rCBF and impaired cerebral autoregulation were apparent immediately after injury.

The effect of MK-801 on extracellular neuroactive amino acids in hippocampus after closed head injury followed by hypoxia in rats.

Increased neuronal vulnerability to ischemia or hypoxia has been demonstrated following traumatic brain injury but not explained. Animal data suggest that neuronal damage after traumatic brain injury is caused mainly by massive glutamate release that activates N-methyl-D-aspartate (NMDA) receptors. Using rat models with controlled closed head injury (CHI) followed by hypoxia, we investigated extracellular concentrations of neuroactive amino acids in the hippocampus by in vivo microdialysis. CHI alone produced an immediate increase of glutamate and taurine; hypoxia alone did not alter amino acid concentrations. CHI followed by hypoxia produced a biphasic increase in extracellular glutamate and taurine, with an immediate peak after CHI and a prolonged plateau after hypoxia. Though changes in gamma-aminobutylic acid (GABA) concentration is also prolonged by combined traumatic and hypoxic insults, it showed less alteration than glutamate. Pre-treatment with dizocilpine maleate (MK-801), a non-competitive NMDA antagonist, did not affect the immediate peak of glutamate after CHI but significantly diminished the prolonged plateau after hypoxia. These findings suggest that traumatic brain injury may increase hypoxic release of glutamate, contributing to increased vulnerability to hypoxia. Our data suggest that MK-801 may be beneficial in preventing secondary neuronal damages by hypoxia.

Intraischemic hypothermia during pretreatment with sublethal ischemia reduces the induction of ischemic tolerance in the gerbil hippocampus.

We examined whether mild brain hypothermia during pretreatment with sublethal 2-min ischemia affected the tolerance to subsequent lethal 5-min ischemia. The neuronal densities in the hippocampal CA1 sector of gerbils preconditioned at mild brain hypothermia (32% of normal) were significantly lower than those in gerbils preconditioned at brain normothermia (70% of normal). 72-kDa heat-shock protein immunoreactivity in the CA1 sector preconditioned at mild hypothermia was reduced. These results suggests that mild brain hypothermia during pretreatment with sublethal ischemia reduces the tolerance to subsequent lethal ischemia.

Repeated hyperbaric oxygen induces ischemic tolerance in gerbil hippocampus.

Hyperbaric oxygen (HBO; 100% oxygen at 2 atmospheres absolute) was administered for 1 h to male Mongolian gerbils either for a single session or every other day for five sessions. Two days after HBO pretreatment, the gerbils were subjected to 5 min of forebrain ischemia by occlusion of both common carotid arteries under anesthesia. Seven days after recirculation, neuronal density per 1-mm length of the CA1 sector in the hippocampus was significantly better preserved in the five-session HBO pretreatment group (n = 10: 175.7 (47.8/mm, 54.9% of normal) than in the ischemic control group (n = 10: 26.2 (11.6/mm, 8.0% of normal) and in the single-session HBO pretreatment group (n = 7: 37.3 (21.7/mm, 11.4% of normal). Immunohistochemical staining for the 72-kDa heat-shock protein (HSP-72) in the CA1 sector performed 2 days following pretreatment revealed that the five-session HBO pretreatment increased the amount of HSP-72 present compared with that in the ischemic control group and in the single HBO pretreatment group. These results suggest that tolerance against ischemic neuronal damage was induced by repeated HBO pretreatment, which is thought to occur through the induction of HSP-72 synthesis.

Polyol content of cerebrospinal fluid in brain-tumor patients.

In order to investigate whether cerebrospinal fluid (CSF) polyols are consumed by brain tissue, the concentration of seven polyols in the CSF and the serum of 30 patients with intracranial tumor and 17 control individuals was measured by gas chromatography. The mean polyol content in the control samples showed that the fructose, inositol, and glucitol levels were significantly greater in CSF than in serum. A comparison of the lumbar CSF from control subjects and 11 patients with malignant tumors exposed to the CSF showed the fructose and inositol levels to be significantly lower (54% and 45%, respectively) and the glucose content to be slightly higher (110%) in the tumor cases. These differences were markedly greater in the ventricular than in the lumbar CSF and greater in patients with tumors exposed to the CSF space than in those with tumors buried in the brain tissue. In ventricular CSF obtained from seven patients with malignant brain tumors before and after radio- and/or chemotherapy, significant increases in fructose (34%) and glucitol (48%) levels were found, but the other polyols did not change significantly. In culture, the human glioblastoma cell growth rate was higher in the medium containing fructose and glucose than in that containing glucose alone. A notable amount of fructose and glucose was consumed by cultured glioblastoma cells. The roles of polyols contained in CSF and the effects of fructose on the growth of cultured glioblastoma cells are discussed in light of these findings and of previous reports.

Selective vulnerability of hippocampal CA3 neurons to hypoxia after mild concussion in the rat.

Immunohistochemical staining for microtubule-associated protein 2 (MAP2) and synaptophysin was used to investigate the effect of hypoxia on hippocampal neurons after mild concussion in the rat. Male Sprague-Dawley rats were divided into four groups: Group 1 (n = 3) was subjected to a mild impact-acceleration closed head injury, group 2 (n = 3) was subjected to 30 min of moderate hypoxia, group 3 (n = 5) was subjected to head trauma followed by 30 min of moderate hypoxia, and group 4 (n = 3) comprised sham-operated controls. All rats were fixed by transcardial perfusion 24 h after insult. No damage was observed in CA1 or CA2 neurons in any of the rats. However, rats in group 3 showed selective damage of hippocampal CA3 neurons manifested by a pycnosis and a marked decrease in MAP2 immunoreactivity. Presynaptic terminals visualized by synaptophysin immunostaining showed no differences among groups. The loss of immunoreactivity for the post-synaptic somal and dendritic protein marker MAP2 from the CA3 subfield 24 h after combined insults indicates an increased vulnerability of pyramidal cells in this brain area.

Local cerebral blood flow and glucose metabolism in chronic focal ischaemia of stroke-prone spontaneously hypertensive rats.

The relationship between local cerebral blood flow (ICBF) and local cerebral glucose metabolism (ICGU) at the chronic stage of focal cerebral ischaemia was assessed in young stroke-prone spontaneously hypertensive rats (SHRSP) following occlusion of the distal middle cerebral artery (MCA). On day 7 following this occlusion, ICBF and ICGU were measured by autoradiographic methods using 14C-iodoantipyrine and 14C-2-deoxyglucose (2DG), respectively. The infarct was limited to the ipsilateral cerebral cortex. A narrow band of increased uptake of 14C-2DG was observed in the border zone at the periphery of infarcted areas. The ICBF in the ischaemic cortex revealed a graded reduction from the ischaemic centre to the surrounding tissues. A significant reduction in ICGU coupled to CBF was also observed in 4 of 13 selected noninfarcted regions ipsilateral to the MCA occlusion. The ischaemic regions had a significant increase in water content. The region with ischaemic oedema was limited to a narrow area compared with the findings regarding ICBF and ICGU. The SHRSP strain has more severe cerebral ischaemia, oedema formation, and metabolic derangement at the chronic stage of focal ischaemia, compared to normo-tensive animals.

Pathologic significance of meningeal enhancement ("flare sign") of meningiomas on MRI.

BACKGROUND: The purpose of this study was to clarify the pathologic features and clinical significance of the meningeal enhancement surrounding meningiomas ("flare sign") on contrast-enhanced T1-weighted magnetic resonance images (MRI). METHODS: The marginal dura mater of tumors was resected from nine cases of meningioma exhibiting a flare sign and used for histopathologic evaluation. RESULTS: Connective tissue proliferation was found in the dura mater in all cases, vascular proliferation was found in three, and tumor cell nests were observed in four cases. In one case, tumor cells were found 4.5 mm from the edge of the tumor. In another case, a meningothelial cell cluster was found. CONCLUSIONS: These results suggest that tumor cell nests are present frequently in dura mater that exhibits the flare sign, and that the dura mater near these lesions should be resected as widely as possible.

Pontine glioma with osteoblastic skeletal metastases in a child.

BACKGROUND: The development of systemic metastases from primary intracranial gliomas is rare. We report here a rare case of pontine glioma with osteoblastic skeletal metastases. CASE: This 12-year-old boy presented with a 4-month history of hoarseness, dysphagia, and a progressively ataxic gait. Cranial computed tomography (CT) and magnetic resonance imaging (MRI) revealed a brain stem tumor that was diagnosed as a low grade glioma by stereotactic biopsy. Twelve months later following chemotherapy and radiotherapy, neurologic examination and neuroradiologic studies disclosed a recurrence of the pontine glioma. Skeletal roentgenograms revealed widespread osteoblastic metastases in the skull, vertebral bodies, pelvis, and long bones. A specimen from the iliac bone demonstrated cells that were immunoreactive glial fibrillary acidic protein (GFAP). DISCUSSION: The mechanism of how glioma cells determine their biologic behavior at bony metastatic sites is not known. Infratentorial gliomas, which occur frequently in young patients and demonstrate active bony metabolism, may stimulate osteoblastic cells, and induce osteoblastic changes.

Delayed neuronal damage following focal ischemic injury in stroke-prone spontaneously hypertensive rats.

We detected the delayed accumulation of 45Ca in the lateral part of the striatum 3 days after distal middle cerebral artery (MCA) occlusion in stroke-prone spontaneously hypertensive rats (SHRSP). However, the mechanism of delayed neuronal damage in the striatum, which is not supplied by the occluded MCA, remains unknown. The aim of this study was to evaluate whether the delayed damage involves alterations in the extracellular release of neurotransmitter monoamines and amino acids. Chronological changes in the distribution of neuronal damage were determined by 45Ca autoradiography. The microdialysis probes were inserted into either the medial or lateral part of the striatum. The dialysate content of monoamines, their metabolites and amino acids was determined by analytical techniques. 45Ca accumulation was detected only in the cortex and corpus callosum by 24 hours postischemia and extended to the pyramidal tract, thalamus and lateral portion of the striatum by 3 days. A 3-fold increase in glutamate content, and a 2-fold increase in dopamine content were observed only in the lateral part of the striatum following ischemia. The results suggest that excessive release of glutamate and dopamine is related to delayed neuronal damage that occurs in the lateral part of the striatum in this ischemic model.

Selective hippocampal damage to hypoxia after mild closed head injury in the rat.

Our previous studies have shown selective neuronal damage in the CA3 region after mild closed head injury (CHI) combined with hypoxia. In the present studies, we examined (1) extracellular concentrations of neuroactive amino acids using in vivo microdialysis technique and (2) neuroactive amino acid binding to their receptors using quantitative autoradiography. Male SD rats were divided into five groups; sham control, mild CHI (sacrificed at 1 h or 24 h after CHI), mild CHI followed by hypoxia (1 h or 24 h). [3H]-Glutamate binding to NMDA receptors, [3H]-muscimol binding to GABAA receptors and [3H]-kainate binding to KA receptors were measured in hippocampus and cortex by quantitative autoradiography. With CHI alone, GLU and TAU levels were transiently increased by 15 min posttrauma. In the CHI with hypoxia, increases in GLU and TAU levels were sustained until 60 min following CHI. GABA level was also increased until 75 min posttrauma Pretreatment of MK-801 significantly diminished the prolonged elevation in GLU and TAU levels. (2) CHI alone did not produce prominent change in the measured receptor binding. When hypoxia was combined with CHI, significant increase in [3H] GLU binding to NMDA receptors and significant decrease in [3H]-muscimol binding to GABAA receptors were observed in CA1 and CA3 at 1 h and 24 h post-insult. These results demonstrate that selective hippocampal damage to hypoxia after mild CHI may be mediated through an increase in NMDA receptor activation and the further release of GLU and that NMDA antagonist may be beneficial in preventing secondary neuronal damage by hypoxia.

Hepatocyte growth factor reduces infarct volume after transient focal cerebral ischemia in rats.

Hepatocyte growth factor (HGF) was originally discovered as a powerful mitogen for hepatocytes. HGF functions both as a neurotrophic factor as well as an angiogenetic factor. Furthermore, HGF has an anti-apoptotic effect on vascular endothelial cells. The present study examined the neuroprotective effect of HGF after transient focal cerebral ischemia in rats, in which an anti-apoptotic and an angiogenetic effect of HGF was assumed to contribute to the reduction of the infarct volume. The intraventricular administration of human recombinant HGF (90 micrograms) significantly reduced the infarct volume after 120 minutes occlusion of both the right middle cerebral artery (MCA) and the bilateral common carotid arteries (CCAs). In a separate series of experiments, we investigated both the anti-apoptotic effect on neurons and the angiogenetic effect of HGF histopathologically. The number of survival neurons and vascular lumina in the HGF group were significantly higher than those in the vehicle group. A large number of TUNEL positive neurons were observed in the inner boundary of the infarct area in the vehicle group, whereas only a few TUNEL positive neurons were observed in a corresponding area in the HGF group. In the HGF group, Bcl-2 protein was obviously represented in survival neurons as well as in vascular endothelial cells and in glial cells subjected to ischemia. These data suggest that HGF prevents apoptotic neuronal cell death by upregulating the production of Bcl-2 protein and by an angiogenetic effect in the central nervous system which affected transient focal cerebral ischemia.

Intraischemic hypothermia during pretreatment with sublethal ischemia reduces the induction of ischemic tolerance in the gerbil hippocampus.

We examined whether mild brain hypothermia during pretreatment with sublethal 2-min ischemia affected the tolerance to subsequent lethal 5-min ischemia. The neuronal densities in the hippocampal CA1 sector of gerbils preconditioned at mild brain hypothermia (32% of normal) were significantly lower than those in gerbils preconditioned at brain normothermia (70% of normal). 72-kDa heat-shock protein immunoreactivity in the CA1 sector preconditioned at mild hypothermia was reduced. These results suggest that mild brain hypothermia during pretreatment with sublethal ischemia reduces the tolerance to subsequent lethal ischemia.

Penetrating injury of the vertebral artery caused by a nail gun: preoperative embolization.

We describe a penetrating injury of the vertebral artery caused by a nail gun. The artery was preoperatively embolized using mechanical detachable coils (MDC).

Effects of naloxone on prolactin-secreting pituitary adenomas.

The investigators assessed the effects of the opioid antagonist naloxone on anterior pituitary hormone release in hyperprolactinemic females with pituitary microadenoma (n = 6) and macroadenoma (n = 7). In those with microadenoma, intravenous bolus injection of naloxone significantly increased serum luteinizing hormone (LH) concentrations but had no significant effect on serum prolactin (PRL), follicle-stimulating hormone, and thyroid-stimulating hormone concentrations. In patients with macroadenoma, naloxone significantly decreased serum LH and serum PRL concentrations. The response of LH to naloxone differed considerably between the two groups of patients. The results suggest that LH and PRL secretion is influenced by changes in endogenous opiates and in gonadotropin-releasing hormone and PRL inhibitory factor due to hypothalamic dysfunction.

The effect of hypoxia on brain edema--the promoting effect of superimposed hypercapnia or hypertension.

The effects of hypoxia and superimposed hypercapnia or hypertension during hypoxia on brain tissue water content, pH, and electric activity were studied in Sprague-Dawley and stroke-prone spontaneously hypertensive rats. Auditory brainstem responses and sensory evoked potentials were recorded during the experiment as the indices for cerebral oxygen metabolism. The brains were removed immediately, 1 day, and 2 days after hypoxic insult for gravimetric study. The brain water content increased in all groups on the 1st and 2nd days after hypoxia. The percentage change from the control water content increased only on the 1st day in hypoxic rats. In contrast, it increased on both the 1st and 2nd days after hypoxia in hypercapnic or hypertensive rats. The evoked potentials of hypoxic and hypercapnic-hypoxic rats showed that peak latencies were prolonged significantly during hypoxia and recovered 1 and 2 days after hypoxia. The brain tissue pH decreased during hypoxia and recovered after hypoxia. This study suggests that brain edema develops within 2 days of hypoxic insult and that superimposed hypercapnia or hypertension promotes the brain edema.

Local cerebral blood flow and glucose metabolism in hydrostatic brain edema.

This study investigated the effect of hydrostatic pressure gradient on the cerebrovascular dynamics and metabolism during the development of brain edema. Hydrostatic brain edema was induced by bolus injection of autologous blood through the common carotid artery in Sprague-Dawley rats. Rats were divided into two groups, with craniectomy (Cr+ group) and without (Cr- group). Animals were sacrificed 0, 24, and 48 hours after hypertensive insult. Brain water content was determined by the gravimetric method. Regional cerebral blood flow and local cerebral glucose utilization were measured by the quantitative autoradiographic method using [14C]iodoantipyrine and [14C]deoxyglucose, respectively. Hypertensive insult produced multifocal lesions stained by Evans blue. Brains from the Cr- group showed a transient increase in water content and no significant change in cerebrovascular dynamics and metabolism. Brains from the Cr+ group showed a pronounced increase in water content which persisted 48 hours later. Misery perfusion was also observed 24 hours after the insult and the cerebrovascular dynamics and metabolism were significantly decreased after 48 hours. These results indicate that an increased hydrostatic pressure gradient enhances tissue damage and causes reopening of the blood-brain barrier.

Giant intracranial aneurysm with rapid thrombus formation and intramural hemorrhage--case report.

A 50-year-old female presented with an unusual giant intracranial aneurysm that showed rapid, spontaneous thrombus formation and subsequent intramural hemorrhage. The thrombus appeared as a homogeneous area on magnetic resonance images, in contrast to the usual heterogeneous appearance. Two months after thrombus formation, the aneurysm had grown and developed intramural hemorrhage. The growth of giant intracranial aneurysms is related to neovascularization and recurrent intramural hemorrhage. The rapid formation of an intra-aneurysmal thrombus may stimulate neovascularization, resulting in intramural hemorrhage and aneurysmal growth.