Role of L-type Ca(2+) channels, sarcoplasmic reticulum and Rho kinase in rat basilar artery contractile properties in a new model of subarachnoid hemorrhage.

We have previously described that L-type Ca(2+) channels' (LTCCs) activation and metabotropic Ca(2+) release from the sarcoplasmic reticulum (SR) regulate RhoA/Rho kinase (ROCK) activity and sustained arterial contraction. We have investigated whether this signaling pathway can be altered in a new experimental model of subarachnoid hemorrhage (SAH). For this purpose, arterial reactivity was evaluated on days 1 to 5 after surgery. A significant increase of basal tone, measured 4 and 60min after normalization, was observed on day 5 after SAH and at 60min on days 2 and 3 after SAH. This phenomenon was suppressed with LTCCs and ROCK inhibitors. We have also studied arterial rings vasoreactivity in response to high K(+) solutions. Interestingly, there were no significant differences in the phasic component of the high K(+)-induced contraction between sham and SAH groups, whereas a significant increase in the sustained contraction was observed on day 5 after SAH. This latter component was sensitive to fasudil, and selectively reduced by low nifedipine concentration, and phospholipase C and SR-ATPase inhibitors. Therefore, our data suggest that the metabotropic function of LTCCs is potentiated in SAH. Our results could provide a new strategy to optimize the pharmacological treatment of this pathological process.

Contractile responses to rat urotensin II in resting and depolarized basilar arteries

The effects of human urotensin II (hUII) on the vascular tone of different animal species has been studied extensively. However, little has been reported on the vasoactive effects of rat urotensin (rUII) in murine models. The aim of the present study was to investigate the effects of rUII on vasoreactivity in rat basilar arteries. Basilar arteries from adult male Wistar rats (300-350 g) were isolated, cut in rings, and mounted on a small vessel myograph to measure isometric tension. rUII concentrations were studied in both resting and depolarized state. To remove endothelial nitric oxide effects from the rUII response, we treated selected arterial rings with Nω-nitro-L-arginine methyl ester (L-NAME). 10 μM rUII produced a potent vasoconstrictor response in rat basilar arteries with intact endothelium, while isometric forces remained unaffected in arterial rings treated with lower rUII concentrations. Although L-NAME did not have a significant effect on 10 μM rUII-evoked contraction, it slightly increased arterial ring contraction elicited by 1 μM rUII. In depolarized arteries, dose-dependent rUII increased depolarization-induced contractions. This effect was suppressed by L-NAME. Our results show that the rat basilar artery has a vasoconstrictor response to rUII. The most potent vasoconstrictor effect was produced by lower doses of rUII (0.1 and 1 μM) in depolarized arteries with intact endothelium. This effect could facilitate arterial vasospasm in vascular pathophysiological processes such as subarachnoid hemorrhage and hypertension, when sustained depolarization and L-type Ca2+ channel activation are present

Contractile responses to rat urotensin II in resting and depolarized basilar arteries.

The effects of human urotensin II (hUII) on the vascular tone of different animal species has been studied extensively. However, little has been reported on the vasoactive effects of rat urotensin (rUII) in murine models. The aim of the present study was to investigate the effects of rUII on vasoreactivity in rat basilar arteries. Basilar arteries from adult male Wistar rats (300-350 g) were isolated, cut in rings, and mounted on a small vessel myograph to measure isometric tension. rUII concentrations were studied in both resting and depolarized state. To remove endothelial nitric oxide effects from the rUII response, we treated selected arterial rings with Nω-nitro-L-arginine methyl ester (L-NAME). 10 µM rUII produced a potent vasoconstrictor response in rat basilar arteries with intact endothelium, while isometric forces remained unaffected in arterial rings treated with lower rUII concentrations. Although L-NAME did not have a significant effect on 10 µM rUII-evoked contraction, it slightly increased arterial ring contraction elicited by 1 µM rUII. In depolarized arteries, dose-dependent rUII increased depolarization-induced contractions. This effect was suppressed by L-NAME. Our results show that the rat basilar artery has a vasoconstrictor response to rUII. The most potent vasoconstrictor effect was produced by lower doses of rUII (0.1 and 1 µM) in depolarized arteries with intact endothelium. This effect could facilitate arterial vasospasm in vascular pathophysiological processes such as subarachnoid hemorrhage and hypertension, when sustained depolarization and L-type Ca(2+) channel activation are present.

The prognostic value of the temporal course of S100beta protein in post-acute severe brain injury: A prospective and observational study.

PRIMARY OBJECTIVE: To study the predictive capacity of early S100beta samples for long-term outcome prediction after severe TBI. METHODS AND PROCEDURES: Eighty-seven patients with severe TBI were studied. Clinical and CT scan were taken at admission. S100beta concentration was quantified at admission and 24, 48 and 72 hours post-TBI (days 0, 1, 2 and 3). Outcome was assessed 12 months after discharge using Glasgow Outcome Score (GOS). RESULTS: Significant negative correlations were found between 1-year GOS and S100beta concentrations on days 1-3, but not on day 0. Deceased patients showed higher S100beta concentration than survivors on days 1-3. Good (GOS = 4-5) vs poor outcome (GOS = 1-3) differed significantly on day 3. Death outcome was independently predicted by day 2 (>2.37 microg l(-1)), day 3 (>1.41 microg l(-1)) samples and absence of pupillary reaction. Poor outcome was predicted independently only by pupillary reaction and the 72-hour sample (>1.1 microg l(-1)), but this predictive model was less satisfactory than the predictive model for death. CONCLUSIONS: A temporal profile of S100beta release from admission to 72 hours post-TBI is strongly recommended for use in identifying patients at risk of developing a worse outcome. The S100beta protein might be an early biomarker for predicting long-term outcome in patients with acute severe TBI.

The role of citicholine in neuropsychological training after traumatic brain injury.

Objective: To report new strategies in the treatment of persistent memory deficits following traumatic brain injury (TBI) using a combination of pharmacology and neuropsychological training. Study design: Two studies were carried out. The first study measured the regional cerebral blood flow (rCBF) of seven Patients with TBI with very severe memory deficits, once while resting and once one hour after the administration of citicholine (CDPc). In the second study, two groups of five patients of the same characteristics underwent an ecological neuropsychological memory rehabilitation program; during which time, one group was administered a placebo (Group A), and the other received CDPc (1~g/d v.o.) (Group B). Results: The results of Experiment 1 showed a hypoperfusion of the inferior left temporal cerebral blood flow during rest state while an induced normalization was observed after administration of the drug. Results of Experiment 2 showed no improvements in Group A's neuropsychological functions, while memory, learning processes and verbal fluency of Group B improved significantly after treatment. Conclusions: CDP-choline seems to be a drug with special affinity for cerebral areas associated with memory acting just where needed, normalizing blood flow in the hypoperfused left temporo-basal region, and making neuropsychological training effective. In general, data suggests that cognitive rehabilitation would follow the principle of first restoring and maintaining cerebral blood flow in the lesional site and then exercising function. In this study on memory rehabilitation, memory recuperation was made possible by first normalizing blood flow at the lesional site and at the same time applying neuropsychological training.