Presynaptic prostaglandin E2 EP1-receptor facilitation of cerebral nitrergic neurogenic vasodilation.

BACKGROUND AND PURPOSE: Prostaglandin E(2) (PGE(2)) modulates autonomic transmission in the peripheral circulation. We investigated the role of endogenous PGE(2) and its presynaptic EP(1) receptor subtype in modulating the autonomic neurotransmission in cerebral vasculature. METHODS: The standard in vitro tissue-bath technique was used for measuring changes in isolated porcine basilar arterial tone. Calcium imaging and nitric oxide estimation along with immunohistochemical analysis for cyclo-oxygenase-1, cyclo-oxygenase-2, EP(1) receptor, PGE synthase, and neuronal nitric oxide synthase were done in cultured sphenopalatine ganglia and basilar artery. RESULTS: Selective EP(1) receptor antagonists (SC-19220 and SC-51322) inhibited relaxation of endothelium-denuded basilar arterial rings elicited by transmural nerve stimulation (2 and 8 Hz) without affecting that induced by nicotine or sodium nitroprusside (a nitric oxide donor). The SC-19220 inhibition of transmural nerve stimulation-elicited relaxation was blocked by cyclo-oxygenase inhibitors (salicylic acid and naproxen) but was not affected by guanethidine (a sympathetic neuronal blocker) or atropine. Perivascular cyclo-oxygenase-1- and cyclo-oxygenase-2-immunoreactive fibers were observed in basilar arteries. PGE synthase and EP(1) receptor immunoreactivities were coincident with neuronal nitric oxide synthase immunoreactivities in perivascular nerves of the basilar arteries and the sphenopalatine ganglia. omega-conotoxin (an N-type calcium channel blocker) significantly blocked transmural nerve stimulation-induced relaxation, which was further attenuated by SC-19220. In cultured sphenopalatine ganglia neurons, exogenous PGE(2) significantly increased calcium influx and diaminofluorescein fluorescence indicative of nitric oxide synthesis. Both responses were blocked by SC-19220. CONCLUSIONS: These results suggest that neuronal PGE(2) facilitates nitric oxide release from the cerebral perivascular parasympathetic nitrergic nerve terminals by increasing neuronal calcium influx through activation of presynaptic EP(1) receptors. PGE(2) may play an important role in regulating the nitrergic neurovascular transmission in the cerebral circulation.

Effect of phospholipase C blockade on cerebral vasospasm.

BACKGROUND: Delayed cerebral ischemia due to cerebral vasospasm remains a major cause of morbidity and mortality following subarachnoid hemorrhage. Oxyhemoglobin (OxyHb) and vasoconstrictor prostanoids have been suggested as putative spasmogens. We have previously reported a synergistic vasoconstrictive action between thromboxane A(2) (TXA(2)) and OxyHb. In the present study we examine the effect of neomycin, a phospholipase C inhibitor, on the cerebral vasoconstriction induced by TXA(2) and OxyHb. METHODS: Using an in vitro tissue bath method, we assess the effect of neomycin in a concentration-dependent manner, on isolated porcine basilar arteries constricted by U-46619 (TXA(2) analogue) and OxyHb. RESULTS: The functional synergism between TXA(2) and OxyHb, leading to significant cerebral vasoconstriction, is attenuated in a dose-dependent manner by neomycin. CONCLUSION: Blockade of phospholipase C may provide an alternative strategy in the treatment of subarachnoid-hemorrhage-induced cerebral vasospasm.

Transsulcal microsurgical approach for subcortical small brain lesions: technical note.

We describe a transsulcal microsurgical approach for removal of small subcortical brain lesions, guided by frameless stereotaxy. This technique of simultaneous stereotactic localization of the subcortical lesion and its adjacent sulcus, before surgical approach, results in optimal surgical planning, leading to minimal brain tissue loss and excellent surgical outcome.

Radiological evaluation of cerebral aneurysms in selected clinical presentations.

BACKGROUND AND PURPOSE: Cerebral aneurysms have different presenting features and, to some extent, a variable clinical course based on the pattern of subarachnoid hemorrhage, the circumstance of their discovery, and the anatomy. Thus, the neuroimaging workup must be tailored accordingly to provide accurate diagnosis and optimal follow-up. METHOD: The authors suggest neuroradiological evaluation of patients in the emergency room and in cases of perimesencephalic subarachnoid hemorrhage, aneurysmal pattern of subarachnoid hemorrhage with normal angiography, vascular infundibula, unruptured/incidental aneurysms, infectious aneurysms, dissecting aneurysms, dolichoectatic/fusiform aneurysms, intracavernous aneurysms, and traumatic aneurysms. CONCLUSION: Recent neuroimaging advances have contributed to improvement in diagnostic safety and accuracy, allowing a more diligent patient follow-up, improved patient outcome, and enhanced physician perception and clinical judgment.

EP1- and EP3-receptors mediate prostaglandin E2-induced constriction of porcine large cerebral arteries.

Prostaglandin E2 (PGE2) has been shown to dilate and constrict the systemic vascular beds, including cerebral vessels. The exact mechanism of PGE2-induced cerebral vasoconstriction, however, is less clarified. The authors' preliminary studies showed that PGE2 exclusively constricted the adult porcine basilar arteries. The present study, therefore, was designed to examine the receptor mechanisms involved in PGE2-induced constriction of large cerebral arteries in the adult pig. Results from an in vitro tissue-bath study indicated that PGE2 and its agonists 17-phenyl trinor PGE2 (17-PGE2), sulprostone (EP1/EP3 receptor agonists), and 11-deoxy-16,16-dimethyl PGE2 (11-PGE2, an EP2/EP3-receptor agonist) induced exclusive constriction, which was not affected by endothelium denudation or cold-storage denervation of perivascular nerves. The constriction induced by PGE2, 17-PGE2, and sulprostone, but not by potassium chloride, was blocked by SC-19220 (a selective EP1-receptor antagonist), AH-6809 (an EP1/EP2-receptor antagonist), and U-73122 and neomycin (phospholipase C inhibitors). AH-6809, however, did not affect 11-PGE2-induced contraction. These results suggest that the contraction was not mediated by the EP2-receptor, but was mediated by EP1- and EP3-receptors. Furthermore, EP1-receptor immunoreactivities were found across the entire medial smooth muscle layers, whereas EP3-receptor immunoreactivities were limited to the outer smooth muscle layer toward the adventitia. Western blotting also showed the presence of EP1- and EP3-receptor proteins in cultured primary cerebral vascular smooth muscle cells. In conclusion, PGE2 exclusively constricts the adult porcine large cerebral arteries. This constriction is mediated by phosphatidyl-inositol pathway via activation of EP1- and EP3-receptors located on the smooth muscle cells. These two receptor subtypes may play important roles in physiologic and pathophysiologic control of cerebral vascular tone.

Role of single photon emission computed tomography and transcranial Doppler ultrasonography in clinical vasospasm.

This report presents our experience with Transcranial Doppler (TCD) ultrasonography and Single Photon Emission Computed Tomography (SPECT) in the assessment of patients with aneurysmal subarachnoid haemorrhage (SAH). It was designed to evaluate clinical vasospasm with both TCD and SPECT and determine their diagnostic value. Twenty-eight consecutive patients were examined with both TCD and SPECT, performed within 24 hours of each other. They had a total of 45 TCDs and 46 SPECT scans. Eight patients (29%) developed clinical vasospasm, noted from day 2 to day 11 post subarachnoid haemorrhage; these patients underwent TCDs and SPECT scans when the diagnosis of vasospasm was made. Twenty patients (71%) did not demonstrate clinical vasospasm throughout their hospital stay and underwent TCDs and SPECT scans within the first 2 weeks of their SAH, mostly between day 2 and day 10, the period of greatest risk for vasospasm. TCD and SPECT sensitivity for clinical vasospasm was 100% and 50% respectively, their specificity was only 20% and 60%. TCD sensitivity for symptomatic vasospasm was found to be excellent, whereas SPECT was not found to be as useful. We conclude that TCD is the preferred method in the evaluation of patients with subarachnoid haemorrhage.