Joji Inamasu

Post-ischemic hypothermia delayed neutrophil accumulation and microglial activation following transient focal ischemia in rats.

Following ischemia, inflammation has been demonstrated to be involved in the progression of the tissue damage. Intra-ischemic hypothermia has been shown to attenuate the adverse activities of neutrophils and microglia. We investigated whether neutrophil accumulation and/or microglial activation is attenuated in post-ischemic hypothermia following transient focal ischemia in rats. After 1 h of ischemia, the neutrophil accumulation and the microglial activation was evaluated immunohistochemically. Percent infarct area was compared at 1, 2, 3, 5, and 7 days after ischemia/reperfusion. In hypothermia, the neutrophil accumulation was delayed but not attenuated. In normothermia, the accumulation reached the peak at 2 days after ischemia. The peak shifted to 3 days in hypothermia. Similarly, the microglial activation was delayed in hypothermia. Comparison of the infarct area showed significant protection by hypothermia at 1 and 2 days after reperfusion. However, hypothermia failed to show significant protection after 3 days and later. These results show that the delayed neutrophil accumulation and the microglial activation can be responsible for the loss of persistent protection in post-ischemic hypothermia.

Postischemic hypothermia inhibits the generation of hydroxyl radical following transient forebrain ischemia in rats.

A small reduction of body temperature during reperfusion following cerebral ischemia has been known to ameliorate neuronal injury. However, the mechanisms underlying postischemic hypothermia-induced neuroprotection are poorly understood. The burst of reactive oxygen species (ROS) formation that occurs during reperfusion has been documented to be involved in ischemic neuronal degeneration. In this study, we investigated the effect of postischemic hypothermia on ROS production following transient forebrain ischemia using an in vivo microdialysis technique. Forebrain ischemia was induced by bilateral carotid artery occlusion combined with hemorrhagic hypotension for 20 min in male Wistar rats. The body temperature was kept at 37 degrees C during ischemia and controlled at either 32 degrees C or 37 degrees C after reperfusion. The amount of hydroxyl radical produced in striatum was evaluated by measurement of 2,3- and 2,5-dihydroxybenzoic acid (DHBA), which is generated by salicylate hydroxylation. We also measured the extracellular concentration of xanthine, while determining striatal blood flow by the hydrogen clearance technique. In animals whose postischemic body temperature was maintained at 37 degrees C, the levels of 2,3- and 2,5-DHBA significantly increased after reperfusion. The peak levels of 2,3- and 2,5- DHBA were 2.9-fold and 2.7-fold increased above the corresponding baseline values, respectively. Postischemic hypothermia completely inhibited the hydroxyl radical formation. Likewise, xanthine formation was also inhibited by postischemic hypothermia. In contrast, striatal cerebral blood flow was not altered by temperature modulation during reperfusion. These results suggest that inhibition of ROS production accompanied with suppression of xanthine formation is implicated in the neuroprotection of postischemic hypothermia.

Postischemic hypothermia attenuates apoptotic cell death in transient focal ischemia in rats.

Hypothermia confers potent neuroprotection against ischemic injury. Attenuation of apoptosis by hypothermia can be one of the responsible mechanisms. In this study, in situ DNA nick-end labeling (TUNEL) and immunostaining of Bax protein were performed to evaluate the effect of postischemic hypothermia on apoptotic cell death, employing rodent transient focal ischemia. Animals received 1 hour of transient focal ischemia. Brain temperature was maintained at 37.5 +/- 0.5 degrees C during ischemia. Immediately after reperfusion, animals were assigned to either a normothermic or hypothermic group. In hypothermia, animals were cooled and brain temperature was lowered to 34.5 +/- 1.0 degrees C. Prolonged hypothermia was maintained for 16 hours and animals rewarmed. In both groups, TUNEL and immunostaining of Bax was performed. In normothermia, the number of TUNEL positive cells reached the peak at 2 days after ischemia and decreased gradually. In hypothermia, the peak was shifted to 3 days after ischemia. The number of TUNEL positive cells in hypothermia was persistently below that of normothermia. Similarly, in hypothermia, immunostaining of Bax showed attenuated immunoreactivity compared with that in normothermia. In conclusion, postischemic hypothermia reduced both the number of TUNEL positive cells and immunoreactivity of Bax, which may be one of the responsible mechanisms with which hypothermia exerts neuroprotection.

Effect of intra-ischemic hypothermia on the expression of c-Fos and c-Jun, and DNA binding activity of AP-1 after focal cerebral ischemia in rat brain

It is unknown whether immediate early gene (IEG) induction and subsequent late gene regulation after ischemia is beneficial or deleterious. The aim of this study was to examine the effect of hypothermia on expression of c-Fos and c-Jun, and AP-1 DNA binding activity, after transient focal cerebral ischemia in rat brain, and clarify the role of IEGs and AP-1 after insults. Male Wistar rats underwent right middle cerebral artery occlusion for 1 h with the intraluminal suture method. During ischemia, animals were assigned to either normothermic (NT) or hypothermic (HT) groups. In the NT group, brain temperature was observed to spontaneously increase to 40 degrees C during ischemia. In the HT group, brain temperature decreased to 30 degrees C. Infarct volume in cortex was decreased in the HT group, compared with that in the NT group (P<0.001). Increased c-Fos immunoreactivity in the cortex was observed at 3 h after reperfusion in the HT, but not the NT group, while c-Jun expression was not affected by HT treatment. There was also a significant increase in AP-1 DNA binding activity at 3 h in the HT group when compared to the NT group (P<0.01). In conclusion, hypothermia decreased cerebral infarction in association with early increases in c-Fos expression and AP-1 DNA binding activity in peri-infarct cortex. It remains to be established whether such responses are a cause or consequence of cell survival, but these results clearly establish that altered transcription is a key feature of tissue spared following hypothermic focal ischemia.

Haemorrhagic venous infarction following the posterior petrosal approach for acoustic neurinoma surgery: a report of two cases

Abstract The authors report two surgical cases with acoustic neurinoma in which haemorrhagic infarction occurred via a compromise in cerebral deep venous outflow. In both cases, surgery was performed via the posterior petrosal approach, and the neurinomas were completely removed. In the first case, the haemorrhagic infarction was considered to have resulted from transection of the tentorial sinus, the presence of which had not been predictable by preoperative angiography. In the second case, the haemorrhagic infarction was caused by a coagulation of the petrosal vein, which was firmly adherent to a tumour. With the posterior petrosal approach, meticulous care is necessary to preserve the deep anastomotic veins into and around the cerebellar tentorium. Thereby, catastrophic morbidity related to compromised deep cerebral venous outflow can be avoided.

Long-term outcome of 17 cases of large-giant posterior fossa aneurysm

Long-term outcome of 17 patients who harbored a large or giant aneurysm of posterior fossa was summarized. The anatomical distribution of aneurysms included eight cases of basilar artery (BA) bifurcation aneurysms, three cases of BA trunk aneurysms, and six cases of vertebral artery (VA) aneurysms. Eight patients received surgical or endovascular treatment for their lesion. The clinical outcome was good recovery in six, moderate disability in one, and vegetative state in one case, respectively. The other nine patients were followed conservatively. Four of them had fatal aneurysmal rupture, and another two patients suffered from aggravation of pre-existing symptoms related to their aneurysm. Only three patients remain intact. Comparison of the radiographic parameters between those who bled and those who did not bleed revealed that those with subsequent rupture had significantly higher rate of aneurysmal thrombus and had a trend for larger diameter of the aneurysm. Although more aggressive and multidisciplinary measure should be taken to these patients to improve their long-term outcome, our results showed the limitation of treatment for these patients in the present era at the same time. The patients with broad neck BA bifurcation aneurysm in which efferent vessels were incorporated into aneurysmal dome, and those with fusiform, giant BA trunk aneurysm with thrombus were the least amenable to treatment in our series.

Selective paralysis of the upper extremities after odontoid fracture: Acute central cord syndrome or cruciate paralysis?

A patient presented with selective paralysis of the arms after having sustained a fall. X-ray of the cervical spine showed a type II odontoid fracture with posterior atlantoaxial dislocation. The diagnosis in the emergency room was cruciate paralysis, which is frequently associated with fractures of axis and/or atlas. However, magnetic resonance imaging (MRI) of the cervical spine revealed a lesion consistent with the acute central cord syndrome (CCS) at the C2-C6 level. The patient underwent posterior atlantoaxial arthrodesis to correct instability and was discharged, without much neurological improvement. Cruciate paralysis has been reported to be associated with fractures of axis and/or atlas, and acute CCS has rarely been associated with the fractures. However, this case illustrates that the lesion responsible for selective paralysis of the upper extremities is not as specific as it had been thought to be, and that it is difficult to accurately identify the level of the cervical cord injury by neurological diagnosis and X-rays alone. Supplementary diagnostic modalities, particularly MRI, are required to make a correct diagnosis and develop a therapeutic strategy.

Glycerol attenuates the adherence of leukocytes in rat pial venules after transient middle cerebral artery occlusion

Intravenous infusion of glycerol has been used in patients with a cerebral infarction, expecting improvement in brain edema and cerebral blood flow (CBF). However, the mechanism of the improvement of CBF has not been clearly demonstrated. The aim of this study in the rat pial microvasculature after transient middle cerebral artery occlusion (MCAO) is to examine the effects of glycerol on leukocyte-endothelium interaction, which plays a critical role in the pathogenesis of brain injury by ischemia/reperfusion and concerns induction of secondary brain damage. Rhodamine 6G-labeled leukocytes at the brain surface were visualized with intra-vital fluorescence videomicroscopy through a closed cranial window and an analysis was made of the number of adherent leukocytes and the centerline leukocyte velocity in the venule before MCAO, after reperfusion of MCAO and after infusion of glycerol (Group 1) or saline (Group 2). The number of adherent leukocytes decreased and the centerline leukocyte velocity increased statistically significantly immediately after the infusion of glycerol in Group 1, but there was no significant change in Group 2. The infusion of glycerol washes away the adherent leukocytes and prevents them from interfering with the blood cell and plasma flow. Furthermore, secondary brain damage may be relieved by decreasing the adherence of leukocytes. In conclusion, modulating the adherence of leukocytes is one of the important factors in the neuroprotective effect of glycerol.

Neuroprotection role of adenosine under hypothermia in the rat global ischemia involves inhibition of not dopamine release but delayed postischemic hypoperfusion

Adenosine (ADO) has an important role in the ischemic brain as an endogenous neuroprotective factor. On the other hand, intraischemic hypothermia ameliorates ischemic neuronal injury. To investigate the effect of ADO during intraischemic mild hypothermia, the extracellular concentration of ADO, its metabolites, dopamine (DA), and local cerebral blood flow were measured in rat striatum during and after 20 min of global ischemia. Additionally, the histopathological outcome was estimated after 48 h of recirculation. Three experimental groups were used: (1) a normothermic group (NT) maintained at 37 degrees C during and after ischemia; (2) a hypothermic group (HT), exposed to intraischemic hypothermia (32.0 degrees C) and postischemic normothermia; and (3) a hypothermia plus theophylline group (HT+T), with the same temperature conditions as in the HT group, combined with intravenously administration of theophylline (10 mg/kg), an antagonist of adenosine receptor, which was given 10 min before ischemia. The level of ADO in HT was significantly higher than ADO levels in NT. In contrast, ischemic DA release was significantly inhibited in HT compared with NT. Theophylline administration had no effect on intraischemic hypothermia induced modulation of extracellular ADO and DA concentration. The postischemic delayed hypoperfusion was ameliorated in HT, and theophylline eliminated this effect in HT+T. A protective effect on histopathological outcome was observed in HT and HT+T. These results suggest that ADO plays an essential role in the inhibition of postischemic delayed hypoperfusion, but this effect is not crucial role in the protective effect induced by intraischemic hypothermia.

Medial (Intra-cisternal) Acoustic Neuromas

The clinical characteristics of medial or intra-cisternal acoustic neuroma (AN) treated in our institute were reviewed. Among 466 patients with ANs in our series during the last 20 years, 6 patients (1.3%) were considered to fill the criteria of medial AN definition. Compared with those with non-medial ANs, the patients with medial ANs show a tendency to have cerebellar and/or cranial nerve dysfunction (especially trigeminal and/or facial nerves) in addition to hearing loss at the time of initial presentation. On magnetic resonance imaging, medial AN is visualized as a multi-cystic mass lesion in the cerebello-pontine cistern without extension into the internal auditory canal in most cases. Although total removal of tumor was achieved in all cases, the results of preservation of facial nerve function were not satisfactory. Medial AN can be considered as a clinical, but not pathological, subtype in terms of the functional outcomes of the facial nerve and hearing.The clinical characteristics of ?medial? or ?intra-cisternal? acoustic neuroma (AN) treated in our institute were reviewed. Among 466 patients with ANs in our series during the last 20 years, 6 patients (1.3%) were considered to fill the criteria of medial AN definition. Compared with those with non-medial ANs, the patients with medial ANs show a tendency to have cerebellar and/or cranial nerve dysfunction (especially trigeminal and/or facial nerves) in addition to hearing loss at the time of initial presentation. On magnetic resonance imaging, medial AN is visualized as a multi-cystic mass lesion in the cerebello-pontine cistern without extension into the internal auditory canal in most cases. Although total removal of tumor was achieved in all cases, the results of preservation of facial nerve function were not satisfactory. Medial AN can be considered as a clinical, but not pathological, subtype in terms of the functional outcomes of the facial nerve and hearing.