Pre, intra and post-ischemic hypothermic neuroprotection in temporary focal cerebral ischemia in rats: morphometric analysis

Abstract

Objective: To evaluate the neuroprotection of mild hypothermia, applied in different moments, in temporary focal cerebral ischemia in rats. Methods: Rats was divided into Control (C), Sham (S), Ischemic-control(IC), Pre-ischemic Hypothermia (IH1), Intra-ischemic Hypothermia (IH2), and Post-ischemic Hypothermia (IH3) groups. Morphometry was performed using the KS400 software (Carl Zeiss IH3 and IH1 vs. IH2 (p=0.57; p=0.79). Conclusion: Pre-ischemic and intra-ischemic hypothermia were shown to be similarly neuroprotective, but this was not true for post-ischemic hypothermia.Key words: brain ischemia, mild hypothermia, morphometry, neuroprotection, reperfusion. RESUMOObjetivo: Avaliar a neuroproteção da hipotermia leve, aplicada em diferentes momentos, durante isquemia cerebral focal temporária em ratos .Métodos: Ratos foram divididos em grupos: Controle (C), Sham (S), Controle-isquêmico (IC), Hipotermia Pré-isquêmica (IH1), Hipotermia Intra-isquêmica (IH2) e Hipotermia Pós-isquêmica (IH3). A morfometria foi realizada em secções coronais coradas por Luxol Fast Blue através do programa KS400 (Carl Zeiss ® ). Foram calculados áreas e volumes isquêmicos. Resultados: Estatisticamente, áreas azuis demonstraram diferença entre os grupos C vs. IC, IC vs. IH1 e IC vs. IH2 (p=0,0001; p=0,01; p=0,03), e nenhuma diferença entre C vs. S, IC vs. IH3 e IH vs. IH2 (p=0,39; p=0,85; p=0,63). Áreas vermelhas demonstraram diferença entre C vs. IC, IC vs. IH1 e IC vs. IH2 (p=0,0001; p=0,009; p=0,03), e nenhuma diferença entre C vs. S, IC vs. IH3 e IH1 vs. IH2 (p=0,48; p=0,27; p=0,68). Áreas isquêmicas médias e volumes isquêmicos demonstraram diferença entre os grupos IC vs. IH1 e IC vs. IH2 (p=0,0001 and p=0,0011), e nenhuma diferença entre IC vs. IH3 and IH1 vs. IH2 (p=0,57; p=0,79). Conclusão: Hipotermias pré-isquêmica e intra-isquêmica demonstraram neuroproteção em grau semelhante, o que não ocorreu com hipotermia pós-isquêmica.Palavras-Chave: isquemia encefálica, hipotermia leve, morfometria, neuroproteção, reperfusão.

Effect of Combination Therapy Using Hypothermia and Granulocyte Colony-Stimulating Factor in a Rat Transient Middle Cerebral Artery Occlusion Model

“…Control ischemic group (n = 8) that submitted to 60 minutes of ischemia [5, 6, 13, 14] and 24 hours of reperfusion and then rats kept for seven days.…”

“…Post-ischemic hypothermia (33.5-35°C) [5] was initiated at the time of reperfusion for 30 minutes, and then rats kept for seven days.…”

“…Body temperature was intermittently recorded using a rectal thermometer (chicco, Australia) and kept between 37 and 38°C using a 220 V lamp next to the animal. Post-ischemic hypothermia was obtained by placing the animals in a container containing ice on neck and temporal region immediately after surgery [5]. The left cervical vessels were exposed through a ventral midline incision under a surgical microscope (Olympus Szx12).…”

“…Cytotoxic edema is a significant clinical problem that can be developed in response to a large middle cerebral artery (MCA) occlusion and has been associated with approximately 80% mortality rate. Cerebral vascular occlusion initiates a sequence of events involving cell swelling [4] and a series of biochemical events with histopathological consequences, which, if not blocked, leads to neuronal death [5]. …”

Effect of local mild hypothermia on regional cerebral blood flow in patients with acute intracerebral hemorrhage assessed by ^{99m}Tc-ECD SPECT imaging

“…However, recent experimental and clinical studies have demonstrated that mild hypothermia is useful for neuroprotection [6,7] and the treatment of cerebral edema [8,9] after acute brain injury, including brain trauma, ischemic stroke, and ICH. Mild hypothermia may reduce cerebral metabolism, decrease levels of excitatory amino acids, stabilize the blood-brain barrier, and account for membrane stabilization [10][11][12]. In mild hypothermia, systemic mild hypothermia is difficult to achieve in clinical practice due to its potential adverse effects, including pneumonia, shivering, and metabolic derangements [8,9], local mild hypothermia can achieve target temperature quickly, and overcome possible adverse effects [13], thus, its efficacy is superior to systemic mild hypothermia in neuroprotective therapies.…”