Taku Shigeno

Cerebral edema following experimental subarachnoid hemorrhage.

The development of cerebral edema after experimental subarachnoid hemorrhage (SAH) was studied in cats by determining regional brain tissue water content with the microgravimetric technique as well as the drying-weighing method. SAH was induced by withdrawing needles previously pierced into one or both infraclinoid internal carotid arteries through a unilateral transorbital approach. Serial determinations of regional cerebral blood flow (rCBF) by labelled microspheres, and monitorings of vital signs such as intracranial pressure (ICP), blood pressure and EEG were carried out up to 24 h after SAH. Animals could be classified into three grades according to the severity of SAH. In grade I, the increase of ICP was transient and minor. In grade II, ICP increased up to 200 mm Hg with a marked reduction of rCBF below 20% of control in cerebral hemispheres. Following subsequent reduction of ICP, rCBF increased over control, indicating reactive hyperemia. Thereafter, a great reduction of rCBF was again observed. In grade III, rCBF was sustained at essentially zero flow with the presence of continuously increased ICP above 100 mm Hg. Cerebral edema was observed particularly in the parasagittal water-shed areas of all grade II animals. It is concluded that cerebral edema complicating SAH is caused by the combination of an initially induced global cerebral ischemia and the subsequent recovery of cerebral circulation. Post SAH hypertension is another factor to exacerbate the development of cerebral edema.

Endothelin-1 Acts in Cerebral Arteries from the Adventitial but Not from the Luminal Side

Summary The in vivo vasoconstrictor effect of endothelin-1 (ET-1) was investigated on feline and canine basilar arteries. The basilar artery caliber was angiographically measured after either vertebral artery perfusion or asternal injection of the peptide. In both cats and dogs, ET-1 (5–500 pmol) induced a dose-dependent basilar artery contraction in vivo when applied intracisternally. The vasoconstriction was extremely long lasting; no significant recovery of vessel caliber was observed up to 12 h after injection. In contrast, bolus injection of ET-1 up to 3 nmol into the vertebral artery had no appreciable effect on the basilar artery caliber. These observations suggest that ET-1 acts in cerebral vessels from the adventitial but not from the luminal side, possibly due to the presence of the blood-brain barrier. The long-lasting nature of the ET-1-induced constriction of the cerebral arteries in vivo suggests that the peptide might be involved in the pathogenesis of cerebral vasospasm.

Endothelins: vasoconstrictor effects and localization in canine cerebral arteries

1 The vascular effects of endothelin and localization of endothelin‐like immunoreactivity were characterized in isolated cerebral arteries of dogs. 2 Endothelin‐like immunoreactivity was detected in a few populations of endothelial cells of dog basilar artery. 3 Endothelin‐1, endothelin‐2 and endothelin‐3 contracted isolated ring preparations of cerebral arteries in a dose‐dependent manner independently of the presence of endothelium. The ED50 values (and 95% confidence intervals) for the contraction were 411 pm (242–697 pm) and 478 pm (295–776 pm) for endothelin‐1 and endothelin‐2, respectively. Endothelin‐3 induced vascular contraction at a higher concentration (ED50 = 26.5 nm, 95% confidence interval = 15.7–45.7 nm). 4 The increases in tone induced by endothelin‐1 and endothelin‐2 did not return to the resting level after repeated washings, while a rinse with Krebs solution reversed the vasoconstrictor response to endothelin‐3. The endothelins did not cause any vasodilator response in arteries precontracted with uridine 5′‐triphosphate even in the presence of intact endothelial cells. 5 NiCl2 (1 mm) attenuated the contractions induced by endothelin‐3 (10–300 nm) and those to relatively low doses (1 nm) but not higher doses (10–100 nm) of endothelin‐1 and endothelin‐2. The contractions in response to endothelin‐1, endothelin‐2 and endothelin‐3 were greatly attenuated in Ca2+‐free solutions although high concentrations of endothelin‐1 and endothelin‐2 still evoked contractions. 6 These results suggest that the vasoconstriction induced by endothelin‐3 and lower doses of endothelin‐1 and endothelin‐2, largely depends on the influx of Ca2+ ions. The apparent insensitivity to Ni2+ shows that additional distinct mechanisms also operate in the vasoconstrictor responses to high concentrations of endothelin‐1 and endothelin‐2. 7 The presence of endothelin‐like immunoreactivity in endothelial cells suggests that endothelin is a potential endogenous spasmogen.

The role of free radicals and eicosanoids in the pathogenetic mechanism underlying ischemic brain edema

Results of our consecutive study on the pathogenic mechanism underlying ischemic brain edema are summarized in this paper. Pertinent findings are as follows: (1) there is a close correlation between the influxes of water and sodium following ischemia; (2) the edema fluid can be regarded as the ultrafiltrate of serum; (3) there is a significant increase in the brain content of HETEs following ischemia; (4) the lipoxygenase activity of brain microvessels is increased following ischemia; (5) the lipoxygenase activity as well as the Na+, K+-ATPase activity of brain microvessels are enhanced by a hydroperoxide, 15-HPETE; (6) inhibition of Na+, K+-ATPase of brain microvessels by intraarterial infusion of ouabain resulted in a significant decrease in edema formation; and (7) not the cyclooxygenase, but the lipoxygenase pathway seems to be involved in the enhancement of microvessel Na+, K+-ATPase. Lipoxygenase(s) and Na+-K+-ATPase of brain microvessels, the activities of which are enhanced by an increased level of free radicals and/or hydroperoxides, may play a significant role in the occurrence of ischemic brain edema.

Significance of nerve growth factor content levels after transient forebrain ischemia in gerbils

Involvement of nerve growth factor (NGF) in the pathogenesis of delayed neuronal death (DND) of CA1 neurons in the hippocampus has been suggested. We measured regional changes in the content of tissue NGF of the hippocampus in the Mongolian gerbil after 5 min forebrain ischemia. The NGF content was found to decrease significantly in the CA3 and dentate regions by 32% two days after ischemia. By contrast in the CA1 region, the level of NGF became significantly elevated by 50% two weeks after ischemia or later. The early reduction of NGF content in the afferent area projecting to the CA1 sector might be primarily linked to the pathogenesis of DND, whereas the delayed increase within the CA1 sector might be a secondary local response mainly of reactive astroglia.

Transcranial approach for transsphenoidal encephalocele: report of two cases

BACKGROUND Whereas the transcranial approach has been regarded as the therapy of choice for transethmoidal encephalocele, its feasibility for transsphenoidal encephalocele has remained controversial, particularly in neonates and infants. CASE REPORT Two cases of transsphenoidal encephalocele operated transcranially are presented. In the first case, this 6-year-old boy underwent a transpalatal operation with repair of a cleft palate in another hospital before admission. Reoperation via the transcranial route was carried out because of postoperative recurrent meningitis. With partial resection of the anterior wall, the encephalocele could be separated from the underlying tissue, and the interspace was filled with the pericranial flap. He made an uneventful recovery and has been well for the past 3 years. The second was a 3-month-old baby with a large encephalocele filling the nasopharyngeal space. As the cleft palate was absent, the transcranial approach was employed. In this case, the herniated tissue was excised at the lowest level possible. Postoperatively, panhypopituitarism became manifest. Re-evaluation of the preoperative magnetic resonance imaging (MRI) disclosed a small mass far below the dorsum sellae, which turned out to be an anomalous pituitary gland on histologic examination. CONCLUSIONS The transcranial approach is considered a valid alternative for the therapy of transsphenoidal encephalocele, particularly when the transpalatal approach is unfeasible. While the anterior wall of the herniated sac may be safely resected, the posterior wall should under no circumstances be sacrificed. The preoperative MRI is essential, as it may provide valuable information as to the location of vital structures within the herniated tissue.

Effect of enhanced capillary activity on the blood-brain barrier during focal cerebral ischemia in cats.

We hypothesize that enhanced activity of capillary Na,K-ATPase promotes Na+ influx into the brain and causes early edema formation in focal cerebral ischemia. The pharmacologic suppression of brain capillary Na,K-ATPase as a means to ameliorate edema formation was examined using the middle cerebral artery occlusion model in 36 cats. With the help of a catheter inserted into the middle cerebral artery, the ischemic brain area was directly perfused with 10(-5) M ouabain. Perfusion was maintained as intermittent 15-second pulse injections given every 5 (n = 6) or 2 (n = 6) minutes. By this method, the naturally occurring circulatory conditions during ischemia were not altered. Four hours after ischemia, the cortical specific gravity at each of six locations over the ischemic area was compared with the corresponding ischemic blood flow measured by the H2 clearance technique. The results show that ouabain perfused every 2 minutes significantly ameliorated edema formation compared with six control cats perfused with Krebs-Ringer solution. In a separate series of experiments, the Na+ flux across the blood-brain barrier was studied by injecting 22NaCl together with an intravascular reference (cobalt-57-labeled microspheres 15 microns in diameter) into the ischemic area. The brain uptake index of 22Na was markedly increased in the ischemic cortex of six control cats; ouabain treatment in six cats suppressed the increase of Na+ influx. The results support our hypothesis that brain capillary Na,K-ATPase activity increases during early focal ischemia, leading to enhanced Na+ together with H2O flux across the blood-brain barrier.

Effects of indomethacin on rCBF during and after focal cerebral ischemia in the cat.

The effect of indomethacin on rCBF was studied in cats anesthetized with Nembutal either under resting conditions or with temporary middle cerebral artery (MCA) occlusion. RCBF was measured by the microsphere method. In control animals (n = 3), indomethacin (4 mg/kg, i.v.) significantly reduced rCBF by about 25% in both cortex (from 44 +/- 6 to 32 +/- 3 ml/100 g/min, p less than 0.001) and white matter (from 36 +/- 4 to 26 +/- 2 ml/100 g/min, p less than 0.001). After MCA occlusion rCBF was markedly decreased in the sylvian region ipsilateral to occlusion (ischemic core) (from 38 +/- 4 to 14 +/- 2 ml/100 g/min in cortex, 4 animals). Although pretreatment with indomethacin (4 mg/kg) (4 animals) 30 min prior to occlusion did not alter rCBF during ischemia, a marked enhancement of reactive hyperemia was observed in the ischemic core immediately upon reperfusion following 2 h occlusion (54 +/- 11 untreated vs 95 +/- 13 treated, p less than 0.05). In the delayed postischemic period, namely 2 h after recirculation, rCBF still remained to be higher in the animals treated with indomethacin (40 +/- 6 untreated vs 96 +/- 9 treated, p less than 0.001). Such an effect of indomethacin for ameliorating postischemic blood flow in both the immediate and delayed period was less prominent in the adjacent area (penumbra) ipsilateral to occlusion. In the contralateral hemisphere, indomethacin caused slight reduction in rCBF during ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Orbitozygomatic approach by transposition of temporalis muscle and one-piece osteotomy

BACKGROUND A more simplified and easier technique for the orbitozygomatic approach is sought. We have developed a new modification to fully expose the temporal base before using one-piece craniotomy. METHODS By transposing the temporalis muscle underneath the zygomatic arch before osteotomy, the temporal base and the inferior orbital fissure can be fully exposed. Craniotomy is made in one piece with the frontotemporal and orbitozygomatic bone together by using a high-speed drill. RESULTS AND CONCLUSIONS Osteotomy was easy and the cosmetic result was satisfactory. This technique also allows better access to the subtemporal region without removing the zygomatic arch.

A Novel Concept on the Pathogenetic Mechanism Underlying Ischaemic Brain Oedema: Relevance of Free Radicals and Eicosanoids

A survey on literature reports and our own experimental studies on the pathogenetic mechanisms underlying ischaemic brain oedema is given and a new concept proposed. In regional incomplete ischaemia the lipoxygenase activity is enhanced, presumably caused by an increase of free radicals and hydroperoxides, leading to an enhancement of endothelial Na+, K+-AtPase and increased sodium and water transport from blood to brain. The aggravation of brain oedema and post-ischaemic hypoperfusion following recirculation appears to be mainly due to an activation of the cyclo-oxygenase pathway with release of oxidants from PGG2, which causes non-specific but detrimental damage to the endothelial and parenchymal cells. This new concept may open future perspectives in treatment which are briefly discussed.