川合 謙介

Preconditioning with sublethal ischemia induces tolerance to subsequent lethal ischemia in neurons. We investigated electrophysiologic aspects of the ischemic tolerance phenomenon in the gerbil hippocampus. Gerbils were subjected to 2 minutes of forebrain ischemia (preconditioning ischemia). Some of them were subjected to a subsequent 5 minutes of forebrain ischemia 2 to 3 days after the preconditioning ischemia (double ischemia). Hippocampal slices were prepared from these gerbils subjected to the preconditioning or double ischemia, and field excitatory postsynaptic potentials were recorded from CA1 pyramidal neurons. Capacity for long-term potentiation triggered by tetanic stimulation (tetanic LTP) was transiently inhibited 1 to 2 days after the double ischemia but then recovered. Latency of anoxic depolarization was not significantly different between slices from preconditioned gerbils and those from sham-operated gerbils when these slices were subjected to in vitro anoxia. Postanoxic potentiation of N-methyl-D-aspartate (NMDA) receptor- mediated transmission (anoxic LTP) was inhibited in slices from gerbils 2 to 3 days after the preconditioning ischemia, whereas it was observed in slices from sham-operated gerbils and gerbils 9 days after the preconditioning ischemia. These results suggest that protection by induced tolerance is (1) not only morphologic but also functional and (2) expressed in inhibiting postischemic overactivation of NMDA receptor-mediated synaptic responses.

Quinolinic acid is an excitotoxic kynurenine pathway metabolite, the concentration of which increases in human brain during immune activation. The present study compared quinolinate responses to systemic and brain immune activation in gerbils and rats. Global cerebral ischemia in gerbils, but not rats increased hippocampus indoleamine-2,3-dioxygenase activity and quinolinate levels 4 days postinjury. In a rat focal ischemia model, small increases in quinolinate concentrations occurred in infarcted regions on days 1,3, and 7, although concentrations remained below serum values. In gerbils, systemic immune activation by an intraperitoneal injection of endotoxin (1 mg/kg of body weight)increased quinolinate levels in brain, blood, lung, liver, and spleen, with proportional increases in lung indoleamine-2,3- dioxygenase activity at 24 h postinjection. In rats, however, no significant quinolinate content changes occurred, whereas lung indoleamine-2,3- dioxygenase activity increased slightly. Gerbil, but not rat, brain microglia and peritoneal monocytes produced large quantities of [13C6]quinolinate from L-[13C6]tryptophan. Gerbil astrocytes produced relatively small quantities of quinolinate, whereas rat astrocytes produced no detectable amounts. These results demonstrate that the limited capacity of rats to replicate elevations in brain and blood quinolinic acid levels in response to immune activation is attributable to blunted increases in local indoleamine- 2,3-dioxygenase activity and a low capacity of microglia, astrocytes, and macrophages to convert L-tryptophan to quinolinate.

モヤモヤ病における頭蓋内出血は、先行するウィリス動脈輪閉塞により血行動態が変化し、二次的に発生すると考えられているが、我々は血管撮影上の変化が一側性かつ非常に軽度の段階で脳室内出血を呈したモヤモヤ病の症例を経験した。症例は19歳日本人男性で入学試験受験中に突然の頭痛で発症。CTで脳室内血腫を認めたが、脳血管撮影では、一側性に内頚動脈遠位部を中心に非常に軽度の狭窄性変化を認めるのみだった。外科的治療は行なわず保存的に経過をみたが、18ヵ月後に再び脳室内出血を来した。この時の脳血管撮影では、両側性にウィリス動脈輪の閉塞⋅狭窄性変化にモヤモヤ血管新生を伴う典型的なモヤモヤ病の所見であった。

A 19-year-old male presented with intraventricular hemorrhage manifesting as sudden onset of headache. Angiography showed mild stenotic changes in the distal internal carotid artery and proximal anterior cerebral artery only on the right. The anterior choroidal artery and lenticulostriate arteries appeared dilated, and an aneurysm-like shadow was seen in the distal right anterior choroidal artery. He was discharged without treatment. Eighteen months later, he presented with a second intraventricular hemorrhage manifesting as sudden occipitalgia, vomiting, and nausea. He had hyperreflexia of the left extremities and paresthesia of the left upper extremity. Angiography showed marked progression of the vascular abnormalities bilaterally. Moyamoya vessels were also present. He received bilateral encephalo-duro-arterio-myo-synangiosis with good results. Moyamoya disease may cause hemorrhage even at an early stage.

We retrospectively evaluated efficacy and risk of external ventricular drainage which was performed in early management of high grade subarachnoid hemorrhage. Acute ventricular drainage was performed on 36.6% of 93 patients with grade V subarachnoid hemorrhage. The percentages of patients whose GCS improved following ventricular drainage were 14.3% from GCS 3, 61.5% from GCS 4, 42.9% from GCS 5 and 42.9% from GCS 6. The occurrence rate of rebleeding was approximately three-fold higher in patients who underwent ventricular drainage than in patients who did not. Aneurysmal surgery performed after ventricular drainage, compared with acute aneurysmal surgery, resulted in the smaller percentage of patients who became persistently vegetative and in the larger percentage of patients who became severely disabled, while it did not change the percentage of patients who resulted in favorable outcome and death. These results of retrospective study suggested that ventricular drainage performed on grade V subarachnoid hemorrhage increased the risk of rebleeding and did not increase the percentage of patients who resulted in favorable outcome although it reduced the percentage of patients who resulted in persistent vegetative state.

We first detected growth-associated protein (GAP-43) immunoreactivity in the neuronal somata following middle cerebral artery occlusion in the rat. Four days after the middle cerebral artery occlusion, GAP-43 immunoreactivity was detected in some cortical neurons of the ischemic penumbra at the level of the hippocampus.

We investigated the protective effect of hypothermia on ultra-early- type ischemic injury in the thalamic reticular nucleus of the rat. Cerebral ischemia was produced by 5 min of cardiac arrest followed by resuscitation. Rectal and cranial temperature during and after cardiac arrest was maintained at 37-38°C in the normothermic group and at 32-33°C in the hypothermic group. In the postischemic hypothermic group, temperature was maintained at 32-33°C starting 15 min after normothermic ischemia. Histological damage was evaluated quantitatively. While after 5 min of recirculation there was no difference in morphological changes in terms of neuronal halo formation, intraischemic hypothermia reduced the severity of the degenerative changes represented by vacuolated or dark neurons by 15 min. Postischemic hypothermia failed to show any evidence of protection by 30 min. The protective effect of intraischemic hypothermia remained significant when evaluated at 14 days after ischemia by volumetry of the lesion and neuronal density analysis, whereas postischemic hypothermia had no clear protective effect. These results suggest that the protective effect of intraischemic hypothermia applies to neurons susceptible to ultra-early-type injury, but the effect of postischemic hypothermia is limited because normothermic ischemia results in extensive degeneration in these neurons by 15 min.

The thalamic reticular nucleus (NRT) is one of the most vulnerable structures to selective neuronal damage both in human cardiac arrest patients and in experimental rodent global cerebral ischemia models. The detailed distribution of neuronal injury within the NRT was examined following 10-min cardiac arrest in the rat with conventional Nissl staining, 45Ca autoradiography and immunocytochemistry of the calcium binding proteins parvalbumin (PV) and calretinin (CR). While Nissl staining was almost unable to show the exact boundary of the nucleus and of the lesion, immunocytochemistry of PV proved to be the most useful index of the exact location and extent of neuronal loss in the NRT after ischemia. Calcium autoradiography was a sensitive method for detecting the lesion, and showed a similar distribution to the loss of PV staining, but did not give optimal spatial resolution. Quantitative analysis of PV staining at 7 days of recirculation demonstrated cell loss restricted to the lateral aspect of the middle segment of the NRT, identical with the distribution of large fusiform neurons in the somatosensory component of the nucleus. CR-positive neurons in the NRT were completely spared, although not all surviving neurons contained CR. These studies provide the first detailed characterization of the distribution of vulnerable neurons within the NRT after experimental ischemia and suggest that immunocytochemistry of PV is a useful tool for quantitative analysis of the lesion for use in further experiments to elucidate the mechanisms of selective vulnerability of the NRT. © 1995 Springer-Verlag.

Astrocytoma arising from the rectum of the mesencephalon is an unusual tumor that is different from other brain stem tumors in clinical features. We describe two patients with tectal low-grade astrocytoma. Each patient underwent CSF diversion and biopsy followed by radiation therapy. A review of the literature on the clinical, radiographic, and pathological findings and the management of rectal tumor is presented.

A 28-year old man presented with diabetes insipidus (DI) 10 days after basilar skull fracture without brain injury. Magnetic resonance (MR) imaging revealed a hematoma in the posterior lobe of the pituitary gland but no lesions in the hypothalamus or pituitary stalk. The patient's DI continued for 2 months at which time transsphenoidal surgery was performed to decompress the cystic hematoma with persistent mass effect. The DI attenuated shortly after the surgery and the patient became completely free from DI 5 months later. Although hemorrhage into the posterior lobe is one of the frequent pathological changes in fatal head-injury victims and secondary DI in these cases has usually been thought to be acute and transient, the true incidence and natural course of the posterior pituitary hemorrhage and subsequent DI in nonfatal head-injury patients are totally unknown. In this article, the authors present the first demonstration on MR imaging of a posterior pituitary hematoma in a patient with head injury. The authors propose that serial MR imaging is an important diagnostic tool in patients with posttraumatic DI because some of them may harbor pituitary hematoma and because decompression surgery may prevent transition to permanent DI, especially in cases when the mass effect is persistent due to a cystic change in the hematoma.

A 42-year-old male presented with a high cervical chordoma detected at an early stage and manifesting only as neck pains. Serial cervical roentgenograms over 8 years confirmed the slow growth character of this malignant tumor. Computed tomography and magnetic resonance imaging provided clear visualization of the tumor localized in the anterior aspect of the C-2 vertebral body. The tumor was totally removed through a transoral approach. Early diagnosis of vertebral chordoma is difficult due to the slow growth character and insidiousness of initial symptoms, but meticulous examination of serial roentgenograms, followed by neuroimaging, can achieve early detection of cervical chordoma. © 1995, The Japan Neurosurgical Society. All rights reserved.

Susceptibility to audiogenic seizures (AGS) was investigated in Sprague- Dawley rats subjected to cardiac arrest cerebral ischemia (CACI), produced by compression of the major cardiac vessels. The onset of AGS was regularly observed 1 day after CACI of &gt 5 min duration. The duration of postischemic susceptibility to AGS was directly related to the density of cerebral ischemia, with 50% of more severely ischemic animals still showing AGS susceptibility 8 weeks after CACI. Lesioning of the inferior colliculi (IC) abolished the onset of AGS no such effect was observed after lesioning the medial geniculate (MG). Glutamic acid decarboxylase (GAD) immunochemistry revealed ~50% loss of GAD-positive neurons in the IC, which was similar in animals with various durations of AGS susceptibility. Otherwise, there was a conspicuous sprouting of γ-aminobutyric acid (GABA)-ergic terminals in the ventral thalamic nuclei, which peaked ~1 month after the CACI. Evaluation of GABA-A inhibitory function in the hippocampus by the paired pulse stimulation revealed changes indicating loss of GABA-A inhibition coinciding with the onset of AGS, and its return in animals tested 2 months after CACI. Our observations suggest a potential role of GABA-ergic dysfunction in the postischemic development of AGS.