Laboratory of Experimental Neuropharmacology, Biological Science Institute, UFPa, Belém, Brazil.
Laboratory of Protozoology, Topical Medicine Nucleus, UFPa, Belém, Brazil.
Front Cell Infect Microbiol. 2020 Sep 30;10:541624. doi: 10.3389/fcimb.2020.541624. eCollection 2020.
Cerebral malaria is characterized by permanent cognitive impairments in -infected children. Antimalarial therapies show little effectiveness to avoid neurological deficits and brain tissue alterations elicited by severe malaria. Melatonin is a well-recognized endogenous hormone involved in the control of brain functions and maintenance of blood-brain barrier integrity. The current study has evaluated the effect of melatonin on the histological alterations, blood-brain barrier leakage, and neurocognitive impairments in mice developing cerebral malaria. Swiss mice infected with ANKA strain was used as cerebral malaria model. Melatonin treatment (5 and 10 mg/kg) was performed for four consecutive days after the infection, and data have shown an increased survival rate in infected mice treated with melatonin. It was also observed that melatonin treatment blocked brain edema and prevented the breakdown of blood-brain barrier induced by the infection. Furthermore, hematoxylin and eosin staining revealed that melatonin mitigates the histological alterations in -infected animals. Melatonin was also able to prevent motor and cognitive impairments in infected mice. Taken together, these results show for the first time that melatonin treatment prevents histological brain damages and neurocognitive alterations induced by cerebral malaria.
脑型疟疾的特征是感染儿童出现永久性认知障碍。抗疟疗法对避免严重疟疾引起的神经功能缺陷和脑组织改变几乎没有效果。褪黑素是一种公认的内源性激素，参与控制大脑功能和维持血脑屏障完整性。本研究评估了褪黑素对发生脑型疟疾的小鼠的组织学改变、血脑屏障渗漏和神经认知障碍的影响。使用感染 ANKA 株的瑞士小鼠作为脑型疟疾模型。在感染后连续 4 天给予褪黑素（5 和 10mg/kg）治疗，结果显示褪黑素治疗可提高感染小鼠的存活率。还观察到褪黑素治疗可阻止脑水肿，并防止感染引起的血脑屏障破裂。此外，苏木精和伊红染色显示褪黑素减轻了感染动物的组织学改变。褪黑素还能预防感染小鼠的运动和认知障碍。综上所述，这些结果首次表明褪黑素治疗可预防脑型疟疾引起的组织学脑损伤和神经认知改变。
