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        Neuroprotective effects of chloroquine on neurological scores, blood-brain barrier permeability, and brain edema after traumatic brain injury in male rats

        Karimi Maryam,Nazari Somayeh,Shirani Faramarz,Alivirdiloo Vahid,Siahposht-Khachaki Ali,Edalatkhah Sepehr,Khanian Rama 대한신경집중치료학회 2023 대한신경집중치료학회지 Vol.16 No.1

        Background: Traumatic brain injury (TBI) is one of leading causes of death among young people worldwide. Chloroquine, an antimalarial drug, has been shown to easily cross the blood-brain barrier (BBB) and inhibit autophagy in a variety of disorders, including Alzheimer disease and brain ischemia. We investigated the effects of chloroquine on neuronal protection after induction of brain trauma in male rats.Methods: A total of 120 male Wistar rats were treated with chloroquine at doses of 1.5, 3, and 6 mg/kg intraperitoneally after induction of diffuse TBIs. The veterinary coma scale was used to assess short-term neurological deficits. BBB disruption was evaluated using the Evans Blue dye method 6-hour post-injury. Vestibulomotor function was evaluated using the beam walk and beam balance methods. Histopathological changes in the brain tissue in different groups were evaluated using light microscopy and hematoxylin-eosin staining. Brain water and cerebrospinal fluid (CSF) contents of matrix metalloproteinase 9 (MMP-9) were assessed using the wet/dry method and enzyme-linked immunosorbent assay, respectively.Results: The results showed that injecting chloroquine (3 and 6 mg/kg) 30 minutes after TBI significantly reduced brain edema and BBB disruption, and recovered neurological deficits post-TBI (P<0.01). Furthermore, CSF MMP-9 was significantly reduced after administration of 1.5 mg/kg chloroquine (P<0.01).Conclusion: Chloroquine has neuroprotective effects in the brain, and thus, has the potential to mitigate the effects of brain trauma. It is possible that the anti-inflammatory and neurogenic effects of chloroquine are due to a decrease in MMP secretion in the CSF.

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