Aydin M, Kislal F M, Ayar A, Demirol M, Kabakus N, Canatan H, Bulmus O, Ozercan R, Yilmaz B, Sen Y, Yoldas T K
Department of Pediatric Neurology, Faculty of Medicine, Firat University, Elazig, Turkey.
Bratisl Lek Listy. 2011;112(5):227-34.
In the present study, the effects of fever and hyperthermia, and different anti hyperthermia treatment modalities on the brain by was investigated by using experimental animal model
Endogenous hyperthermia (41 degrees C) was induced by lipopolysaccharide (LPS) injection, and the signs of probable neuronal damage were evaluated by healthy, necrotic and apoptotic cells, and heat-shock proteins (HSP 27 and HSP 70) in cerebral cortex, cerebellum and hypothalamus. The animals were treated with widely used treatment modalities for high fever in pediatric practice, namely hypothermia, dexamethasone, paracetamol and diclofenac, and their effect on the hyperthermia-induced brain changes were evaluated.
Generalized seizure was observed in fifteen rats of which rectal temperature achieved 41 degrees C (15/36, 41%); five of them died on second day (5/15, 33%). LPS-induced endogenous hyperthermia; (i) caused significant increase of necrotic cells in cerebral cortex and cerebellum and apoptotic cells in all three regions (p < 0.05), (ii) caused significant decrease of healthy cells in cerebral cortex (p < 0.05), and (iii) no significant change of HSP 27 and 70 in all three neuronal locations (p > 0.05). For the treatment modalities applied; (i) paracetamol had an effect of increasing the healthy cell count in cerebral cortex and hypothalamus and decreasing the necrotic cell count in cerebellum and hypothalamus (p < 0.05).
The neuronal tissue in different regions of brain can show various degrees of damage in response to endogenous hyperthermia and the applied medications have varying degree of protection (Tab. 3, Fig. 6, Ref. 44).
在本研究中,通过使用实验动物模型,研究了发热和高热以及不同的抗高热治疗方式对大脑的影响。
通过注射脂多糖(LPS)诱导内源性高热(41℃),并通过大脑皮层、小脑和下丘脑的健康细胞、坏死细胞和凋亡细胞以及热休克蛋白(HSP 27和HSP 70)来评估可能的神经元损伤迹象。对动物采用儿科实践中广泛使用的高热治疗方式,即低温、地塞米松、对乙酰氨基酚和双氯芬酸进行治疗,并评估它们对高热诱导的大脑变化的影响。
在36只大鼠中有15只出现全身性惊厥,其直肠温度达到41℃(15/36,41%);其中5只在第二天死亡(5/15,33%)。LPS诱导的内源性高热:(i)导致大脑皮层和小脑坏死细胞显著增加,以及所有三个区域的凋亡细胞显著增加(p < 0.05),(ii)导致大脑皮层健康细胞显著减少(p < 0.05),以及(iii)在所有三个神经元位置HSP 27和70无显著变化(p > 0.05)。对于所应用的治疗方式:(i)对乙酰氨基酚具有增加大脑皮层和下丘脑健康细胞数量以及减少小脑和下丘脑坏死细胞数量的作用(p < 0.05)。
大脑不同区域的神经元组织对内源性高热可表现出不同程度的损伤,且所应用的药物具有不同程度的保护作用(表3,图6,参考文献44)。