Motohiko Shimazu

Expression of c-fos in the rat cerebral cortex after focal ischemia and reperfusion.

Time-dependent changes in c-fos-like immunoreactivity (c-fos-LI) were studied in the rat during focal cerebral ischemia and reperfusion after middle cerebral artery (MCA) occlusion. In the permanent ischemia model, the levels of c-fos-LI increased for the first 30 min of ischemia in neuronal nuclei in the lesioned hemisphere. They reached a maximum at 60 min. The level in the parietal cortex (PC) diminished considerably after 120 min, and in the cingulate cortex (CC) it gradually decreased to near the control value at 180 min. Regional cerebral blood flow (rCBF) in the PC fell to 32% and that in the CC fell to 64% of pre-ischemic values after MCA occlusion. Reperfusion induced strong expression of c-fos-LI in the PC and CC after 6 h of reperfusion that followed 30 min of ischemia. The c-fos-LI was effectively reduced by preadministration of the N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine (100 mg/kg, IP). These findings suggest that the expression of c-fos after ischemia may be immediately activated through NMDA receptors and may spread to surrounding regions in a manner sensitive to reductions in rCBF. Reperfusion after ischemia also appears to cause activation of expression of c-fos and of intracellular signal transduction.

Sumatriptan Scavenges Superoxide, Hydroxyl, and Nitric Oxide Radicals: In Vitro Electron Spin Resonance Study

Background.—The molecular mechanisms of migraine have not yet been clarified. Oxygen free radicals have been implicated in the genesis of many pathological processes, including migraine. Sumatriptan succinate is known to be a very effective drug for acute relief of migraine attack.

Silent mixed corticotroph and somatotroph macroadenomas presenting with pituitary apoplexy.

Abstract. We discuss three unique cases of pituitary macroadenoma presenting with pituitary hemorrhage but without typical endocrine symptomatology. Immunohistochemical analysis indicated positive reactivity for adrenocorticotropic hormone (ACTH) and growth hormone (GH), and in situ hybridization indicated the expression of proopiomelanocortin (POMC) and GH mRNA. We designated these cases silent mixed corticotroph and somatotroph adenoma. Patient 1 was a 30-year-old man, patient 2 was a 29-year-old woman, and patient 3 was a 59-year-old woman. All patients presented with a headache of sudden onset and visual disturbance. The patients did not exhibit typical Cushings or acromegalic features. Serum ACTH level was remarkably elevated in patient 1, and slightly elevated in patients 2 and 3. In all patients, serum GH levels were within normal range and magnetic resonance imaging revealed an intra- and suprasellar mass with pituitary hemorrhage. Transnasal pituitary surgery in the three patients disclosed a pituitary adenoma producing ACTH and GH. In patient 2, the residual adenoma reappeared along with an intratumoral hemorrhage, and was resected by secondary transnasal surgery. Silent mixed corticotroph and somatotroph adenomas are characterized by the following: no endocrine symptoms; presentation dominated by mass effect symptoms; macroadenoma presenting with acute pituitary hemorrhage; and production of both ACTH and GH.

Trochlear nerve neurinoma associated with a giant thrombosed dissecting aneurysm of the contralateral vertebral artery

The authors encountered the unusual case of a 57-year-old man with a right trochlear nerve neurinoma associated with a giant thrombosed dissecting aneurysm of the left vertebral artery. The right trochlear nerve neurinoma was subtotally removed via the right subtemporal transtentorial route. The trochlear nerve entered the tumor directly posterolaterally. The left vertebral artery was clipped just proximal to the thrombosed dissecting aneurysm via the left lateral suboccipital approach. The patient was discharged without neurologic deficits except for the right trochlear nerve palsy. To our knowledge, this seems to be the first reported case of such an occurrence.

Haemorrhagic Nonsecreting Pituitary Adenoma Associated with Persistent Primitive Trigeminal Artery

A 44-year-old man presented with headache of sudden onset and visual disturbance. There was no personal or family history of neurological disease. Physical examination revealed decreased libido, pale skin, sparse axillary hair, and erection disorder. Neurological examination was normal except for a bitemporal hemianopsia. Endocrinological examination showed panhypopituitarism. A sellar tomogram showed an enlarged sella turcica. A computed tomographic (CT) scan revealed an iso-density mass with ring enhancement in the intraand suprasellar lesion. Magnetic resonance (MR) imaging demonstrated an intraand suprasellar mass with intratumoural haemorrhage, and a vascular structure arising from the left cavernous carotid artery (Fig. 1). No anomalous vascular structure in the pituitary fossa was observed on CT scan and MR imaging. Cerebral angiography showed a persistent primitive trigeminal artery (PPTA) from the left cavernous internal carotid artery which supplied the posterior cerebral arteries, bilaterally, superior cerebellar arteries, and the distal basilar artery (Fig. 2). This tumour was preoperatively diagnosed as a haemorrhagic nonsecreting pituitary adenoma. The patient underwent urgent transsphenoidal surgery. Tumour tissue in the haematoma was subtotally resected. The PPTA was not found in the pituitary fossa. Histological examination showed a di ̈use type chromophobic pituitary adenoma and immunohistochemical study revealed a null cell adenoma. The postoperative course was uneventful. Acta Neurochirurgica > Springer-Verlag 2000 Printed in Austria Acta Neurochir (Wien) (2000) 142: 1423±1424

Time-dependent changes of vasoactive substances in rat cerebral ischemia.

Time-dependent changes in the tissue concentration of tyrosine hydroxylase (TH), adrenaline (A), noradrenaline (NA), and neuropeptide Y (NPY) in the early stages of cerebral ischemia were studied immunohistochemically in the amygdaloid complex of rats subjected to 1 h cerebral ischemia. Immunoreactivity to TH on the lesioned side reached a nadir at 12 h after cerebral ischemia, then gradually increased over 24 h to normal reactivity, but TH immunoreactivity between the ischemic side and the contralateral side was no different for up to 12 h after ischemia. The blood concentrations of NA and A were elevated to about twice the control concentration 12 h after ischemia, then gradually decreased back to normal. NPY immunoreactivity of both sides did not change for up to 6 h after ischemia, but NPY immunoreactivity on the lesioned side decreased over 12 h and maintained a plateau. These findings suggest that responses to cerebral ischemia between catecholamines and peptides are varied.

Protective effect of bifemelane on c-Fos-like immunoreactivity in rat cerebral ischemia.

Cytoprotection by bifemelane hydrochloride was investigated immunohistochemically in the cerebral cortex of rats during ischemia. The middle cerebral artery was occluded for 30 min and then reperfused for 6 h. c-Fos-like immunoreactive neurons were found in layers II to VI of the cerebral cortex and were especially abundant in the parietal cortex and the piriform cortex on the side of the occlusion. In sham-operated control rats, a few c-Fos-like immunoreactive neurons were seen in the ipsilateral side of the cerebral cortex. In animals that had been injected with bifemelane hydrochloride (20 mg/kg, IP) 30 min before the onset of ischemia and 90 min after reperfusion, the number of c-Fos-like immunoreactive neurons was significantly reduced in the cerebral cortex. The results suggest that bifemelane hydrochloride can inhibit the ischemia-induced increase in c-Fos-like immunoreactivity in cerebral cortex neurons.

Morphological changes of c-Fos-like immunoreactivity in rat cerebral cortex after cerebral ischemia and reperfusion with special reference to vasoactive intestinal polypeptide

We investigated morphological changes in neurons with c-Fos-like immunoreactivity (c-Fos-LI) after cerebral ischemia by light and electron microscopic immunocytochemistry. Strong c-Fos-LI was observed in layers II–VI of the cerebral cortex with an especially abundant distribution in the nuclei of layers II, IV, and VI ipsilateral to the lesioned side. Reperfusion after ischemia had a greater effect on the expression of c-Fos-LI than did permanent ischemia. Vasoactive intestinal peptide (VIP)-positive neurons were seen scattered in layers II–V of the cerebral cortex. Some VIP-positive neurons showed c-Fos-LI after ischemia. Electron microscopy revealed c-Fos-LI in euchromatin in the nuclei of c-Fos-positive cells. Dilatation of the cisternae of the rough endoplasmic reticulum and the presence of numerous secondary lysosomes were found in neurons on the lesioned side after 12h of reperfusion. Some VIP-containing neurons revealed c-Fos-LI with reperfusion after ischemia by a double immunostaining method on the same tissue section. These findings suggest that ischemia potentiates c-fos expression in VIP- or other transmitter- or modulator-containing neurons, thereby protecting from neuronal cell death.