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Abstract: We examined in a rabbit model of transient spinal cord ischemia (SCI) whether isoflurane (Iso) preconditioning induces ischemic tolerance to SCI in a dose–response manner, and whether this effect is dependent on mitochondrial adenosine triphosphate-dependent potassium (KATP) channel. Eighty-six rabbits were randomly assigned to 10 groups: Control group (n =8) received no pretreatment. Ischemic preconditioning (IPC) group (n =8) received 5min of IPC 30min before SCI. The Iso 1, Iso 2 and Iso 3 groups (n =10, 9, 8) underwent 30min of 1.05, 2.1 and 3.15% Iso inhalation commencing 45min before SCI. The Iso 1HD, Iso 2HD and Iso 3HD groups (n =9, 9, 8) each received a specific mitochondrial KATP channel blocker, 5-hydroxydecanoic acid (5HD, 20mg/kg), 5min before each respective Iso inhalation. The 5HD group (n =8) received 5HD without Iso inhalation. The sham group (n =9) had no SCI. SCI was produced by infra-renal aortic occlusion via the inflated balloon of a Swan–Ganz catheter for 20min. The Iso 1, Iso 2 and Iso 3 groups showed a better neurologic outcome and more viable motor nerve cells (VMNCs) in the anterior spinal cord 72h after reperfusion than the control group (p <0.05). Iso 3 group showed a better neurologic outcome and more VMNCs than Iso 1 group (p <0.05). And, the Iso 1, Iso 2 and Iso 3 groups showed a better neurologic outcome and higher VMNC numbers than the corresponding Iso 1HD, Iso 2HD and Iso 3HD groups (p <0.05). This study demonstrates that Iso preconditioning protects the spinal cord against neuronal damage due to SCI in a dose–response manner via the activation of mitochondrial KATP channels. [Copyright &y& Elsevier]

This study investigated the neuroprotective effect of pravastatin administration after forebrain ischemia in rats. Forebrain ischemia was induced by bilateral common carotid artery occlusion and systemic hypotension for 8 min. Pravastatin at 1 mg/kg (pravastatin group, n = 10), or an identical volume of normal saline (control group, n = 10), was injected 10 min, and 1–4 days after reperfusion. Arterial blood gas was analyzed 10 min before ischemia onset and 10 min after ischemia completion. Viable and apoptotic neuronal cells were evaluated 7 days after ischemia by hematoxylin and eosin (H&E) staining and terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuracil triphosphate biotin in situ nick-end labeling (TUNEL) staining of the hippocampal Cornu Ammonis area (CA1). Expression of Bcl-2 and Bax proteins was quantified by Western blot analysis. The proportion of viable neuronal cells after ischemia was greater in the pravastatin vs . control group ( p < 0.01), with greater expression of apoptotic cells in the control vs . pravastatin group ( p < 0.05). Bax protein expression was significantly decreased in the pravastatin group ( p < 0.05), whereas, Bcl-2 expression was increased, but not significantly ( p > 0.05). Our findings suggest that pravastatin administration after forebrain ischemia confers neuroprotection in rats by inhibiting Bax protein expression. [ABSTRACT FROM AUTHOR]

Dexmedetomidine (DXM) has anti-inflammatory effects, which is considered an important mechanism of DXM-induced neuroprotection from cerebral ischemia/reperfusion injury. We determined whether the anti-inflammatory effects of DXM are associated with inhibition of the toll-like receptor (TLR)-4/nuclear factor kappa B (NF-κB) pathway in a rat model of transient global cerebral ischemia/reperfusion injury. Fifty rats were randomly assigned to one of five groups (10 rats/group): Group S received no treatment; Group C underwent transient global ischemia (10 min); Group D received DXM 30 min before ischemia; Group R received resatorvid, a selective TLR-4 antagonist, 30 min before ischemia; and Group RD received resatorvid and DXM 30 min before ischemia. The numbers of necrotic and apoptotic cells and the levels of TLR-4, NF-κB, and caspase-3 were assessed 1 day after ischemia, and pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) were measured before ischemia and 2, 6, and 24 h thereafter. The necrotic and apoptotic cell counts and levels of TLR-4, NF-κB, and caspase-3 were higher in Group C than in other groups. TNF-α were higher in Group C than in other groups 2 h after ischemia, whereas IL-6 were higher in Group C 6 h after ischemia. IL-1β was higher in Group C than in Group D 6 and 24 h after ischemia. Our findings suggest that the anti-inflammatory action of DXM via inactivation of the TLR-4/NF-κB pathway, in part, may explain DXM-induced neuroprotection after cerebral ischemia. [ABSTRACT FROM AUTHOR]