Analysis of the protective effects of a neuronal Cav2.1 calcium channel in brain injury.

We previously reported that rolling Nagoya mice carrying a mutation in the α1 subunit of the Cav2.1 channel protective from ischemia- and kainate-induced neuronal damage. However, the protective effect of this mutation and its relationship to brain injury recovery have not been examined. To examine the relationship between Cav2.1 channel function and brain injury, we induced cryogenic brain damage in homozygous rolling Nagoya (rol/rol), control wild-type (+/+), ω-agatoxin IVA-pretreated +/+ (ω-aga +/+), and ω-agatoxin IVA-post-treated +/+ (ω-aga-post-treated +/+) mice. We measured the lesion area, blood brain-barrier permeability and performed immunohistochemistry and western blot analysis. The lesions of rol/rol and ω-aga +/+ mice were significantly smaller than those observed in +/+ mice at both day 1 and day 7 after injury. Similar results were shown in blood-brain barrier permeability. We observed more reactive astrogliosis in +/+ mice than in rol/rol or ω-aga +/+ mice. rol/rol and ω-aga +/+ mice had fewer degenerating cells due to cryogenic injury than did +/+ mice at both day 1 and day 7. ω-Aga-post-treated +/+ mice 24h after injury were sacrificed on day 7. The lesions were smaller in ω-aga-post-treated +/+ mice than those in vehicle-treated +/+ mice. We also examined phosphorylated p38 (pp38) at the injured site. ω-Aga-post-treated +/+ mouse brain slices showed weak pp38 signal; vehicle-treated +/+ mouse brain slices were pp38-positive. These findings demonstrate that the mutant Cav2.1 channel exerts a protective effect against cryogenic brain injury in rolling Nagoya mice. Our results indicate that inhibitors of the Cav2.1-dependent p38 signaling cascade would be useful as therapeutic agents in the treatment of brain injury.

Does Propofol Improve Postischemic Myocardial Dysfunction by Reducing the Postischemic Adhesion of Polymorphonuclear Neutrophils? / 대한마취과학회지

BACKGROUND: Fluid replacement after hemorrhage usually results in hemodilution, and hemodilution leads to increased cerebral blood flow, which is known to be beneficial to the outcome of ischemic brain damage. However, the effect of hemodilution may be different in patients with head injuries and increased intracranial pressure (ICP). The aim of this study was to evaluate the effects of normovolemic hemodilution on cerebral blood flow (CBF), brain tissue oxygen tension (PbtO2), and the severity of cryogenic brain injury, and to determine the acceptable limit of hemodilution during cryogenic brain injury. METHODS: Thirty New Zealand white rabbits were anesthetized with O2-N2O-isoflurane. Cryogenic brain injury (1 cm in diameter) was produced by applying liquid nitrogen on the surface of the right parietal bone for 90 seconds. Sixty minutes after cryogenic brain injury, acute normovolemic hemodilution was induced with 10% pentastarch for 30 minutes. In group I (n = 7), hemodilution was not induced. In groups II (n = 7), III (n = 8), and IV (n = 8), the hemoglobin concentrations were adjusted to 9-10, 6-7 and 3-4 g/dl, respectively. Mean arterial pressure, central venous pressure and ICP were measured, and local CBF and PbtO2 of the right parietal subcortex were continuously monitored. The rabbits were euthanized 150 minutes after brain injury, and the brains were removed and sectioned coronally through the center of the lesion. The extent of brain injury in the coronal plane was measured by light microscopic examination. The posterior part of the brain was divided into two halves and the water fraction of each part was measured by the dry-weight method. Data obtained were compared by the Kruskal-Wallis test or by repeated measures ANOVA. The difference was considered significant when P <0.05. RESULTS: No differences were observed in mean arterial pressure, central venous pressure or rectal temperature. However, significant differences were found in ICP, CBF and PbtO2 among the groups. ICP was significantly higher in group IV than in groups I and II. The CBF values of groups III and IV were higher than those of group I. The values of PbtO2 of group IV were lower than those of groups I and II. Normovolemic hemodilution, of up to 6-7 g/dl of hemoglobin, led to an abrupt increase in CBF and a subsequent increase in ICP. Hemodilution, of up to 3-4 g/dl of hemoglobin, decreased brain tissue oxygen tension significantly. No differences in the brain water fractions and the extent of cryogenic injury were found among the groups. CONCLUSIONS: It is concluded that the acceptable limit of acute normovolemic hemodilution in cryogenic brain injury is 9-10 g/dl of hemoglobin, as ICP and CBF do not increase and PbtO2 does not deteriorate.