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KMID : 1201420230160010018
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Journal of Neurocritical Care
2023 Volume.16 No. 1 p.18 ~ p.27
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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
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Maryam Karimi
Somayeh Nazari
Faramarz Shirani
Vahid Alivirdiloo
Ali Siahposht-Khachaki
Sepehr Edalatkhah
Rama Khanian
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Abstract
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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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KEYWORD
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Chloroquine, Brain trauma, Neural protection
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