Abstract
BackgroundThis study aimed to evaluate the effects of the Acorus tatarinowii Schott [Shi Chang Pu (SCP)] extract administered at the start of 2 h of middle cerebral artery occlusion (MCAo), followed by 3 d of reperfusion, and to determine mechanisms involved in anti-edema effects in the penumbra of the cerebral cortex.MethodRats were intraperitoneally administered the SCP extract at a dose of 0.25 g/kg (SCP-0.25 g), 0.5 g/kg (SCP-0.5 g), or 1 g/kg (SCP-1 g) at the start of MCAo.ResultSCP-0.5 g and SCP-1 g treatments effectively reduced the cerebral infarct size, ameliorated cerebral edema, reduced blood–brain barrier permeability, and restored neurological function. SCP-0.5 g and SCP-1 g treatments markedly downregulated the levels of glial fibrillary acidic protein, Na+-K+-2Cl− cotransporter type 1 (NKCC1), aquaporin 4 (AQP4), phospho-c-Jun N-terminal kinase (p-JNK)/JNK, inducible nitric oxide synthase (iNOS), 3-nitrotyrosine, intercellular adhesion molecule-1 (ICAM-1), matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor-A (VEGF-A), and zonula occluden-1 (ZO-1) and upregulated ZO-3 expression in the penumbra of the cerebral cortex 3 d after reperfusion.ConclusionsSCP-0.5 g and SCP-1 g treatments exert neuroprotective effects against cerebral infarction and cerebral edema partially by mitigating astrocytic swelling and blood–brain barrier disruption. Moreover, the anti-cerebral edema effects of SCP extract treatments are possibly associated with the downregulation of astrocytic NKCC1/AQP4 and JNK/iNOS-mediated ICAM-1/MMP-9 signaling in the penumbra of the cerebral cortex 3 d after reperfusion.
Highlights
This study aimed to evaluate the effects of the Acorus tatarinowii Schott [Shi Chang Pu (SCP)] extract administered at the start of 2 h of middle cerebral artery occlusion (MCAo), followed by 3 d of reperfusion, and to determine mechanisms involved in anti-edema effects in the penumbra of the cerebral cortex
The anticerebral edema effects of SCP extract treatments are possibly associated with the downregulation of astrocytic Na+-K+-2Cl− cotransporter type 1 (NKCC1)/Aquaporin 4 (AQP4) and Jun Nterminal kinase (JNK)/inducible nitric oxide synthase (iNOS)-mediated intercellular adhesion molecule-1 (ICAM-1)/matrix metalloproteinase-9 (MMP-9) signaling in the penumbra of the cerebral cortex 3 d after reperfusion
The SCP extract administered at doses of 0.5 g/kg (SCP-0.5 g) and 1 g/kg (SCP-1 g), but not 0.25 g/kg (SCP-0.25 g), markedly reduced cerebral areas and effectively restored neurological function
Summary
This study aimed to evaluate the effects of the Acorus tatarinowii Schott [Shi Chang Pu (SCP)] extract administered at the start of 2 h of middle cerebral artery occlusion (MCAo), followed by 3 d of reperfusion, and to determine mechanisms involved in anti-edema effects in the penumbra of the cerebral cortex. Cerebral edema is classified into two types: cytotoxic (intracellular) and vasogenic (extracellular) edema; edema results from water transport impairment in cells and blood vessels [2, 5]. In the early phase of cerebral ischemia, the levels of intracellular Ca++ and extracellular K+ are markedly increased in the ischemia area; subsequently, this leads to NKCC1mediated Na+, K+, and Cl− transport and accompanying water influx into brain cells, leading to astrocytic swelling, cytotoxic edema, and cerebral infarction [9, 10]. NKCC1- and AQP4-mediated astrocytic swelling leads to glutamate-mediated excitotoxicity, excessive nitric oxide (NO) production, and cytokine [such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α] release, which subsequently promote BBB disruption in the ischemic area, resulting in exacerbation of cerebral edema [11, 12]. The expression of glial fibrillary acidic protein (GFAP), a marker of reactive astrogliosis, in the ischemic region is positively correlated with the severity of cerebral edema [9, 13, 14]
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