Cargando…
Leucine Reduced Blood–Brain Barrier Disruption and Infarct Size in Early Cerebral Ischemia-Reperfusion
A disruption of the blood–brain barrier (BBB) is a crucial pathophysiological change that can impact the outcome of a stroke. Ribosomal protein S6 (S6) and protein kinase B (Akt) play significant roles in early cerebral ischemia-reperfusion injury. Studies have suggested that branched-chain amino ac...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10605042/ https://www.ncbi.nlm.nih.gov/pubmed/37891741 http://dx.doi.org/10.3390/brainsci13101372 |
_version_ | 1785126978998763520 |
---|---|
author | Chi, Oak Z. Liu, Xia Magsino, Jedrick Weiss, Harvey R. |
author_facet | Chi, Oak Z. Liu, Xia Magsino, Jedrick Weiss, Harvey R. |
author_sort | Chi, Oak Z. |
collection | PubMed |
description | A disruption of the blood–brain barrier (BBB) is a crucial pathophysiological change that can impact the outcome of a stroke. Ribosomal protein S6 (S6) and protein kinase B (Akt) play significant roles in early cerebral ischemia-reperfusion injury. Studies have suggested that branched-chain amino acids (BCAAs) may have neuroprotective properties for spinal cord or brain injuries. Therefore, we conducted research to investigate if leucine, one of the BCAAs, could offer neuroprotection and alter BBB disruption, along with its effects on the phosphorylation of S6 and Akt during the early phase of cerebral ischemia-reperfusion, specifically within the thrombolytic therapy time window. In rats, ten min after left middle cerebral artery occlusion (MCAO), 5 µL of 20 mM L-leucine or normal saline was injected into the left lateral ventricle. After two hours of reperfusion following one hour of MCAO, we determined the transfer coefficient (K(i)) of (14)C-α-aminoisobutyric acid to assess the BBB disruption, infarct size, and phosphorylation of S6 and Akt. Ischemia-reperfusion increased the K(i) (+143%, p < 0.001) and the intra-cerebroventricular injection of leucine lowered the K(i) in the ischemic-reperfused cortex (−34%, p < 0.001). Leucine reduced the percentage of cortical infarct (−42%, p < 0.0001) out of the total cortical area. Ischemia-reperfusion alone significantly increased the phosphorylation of both S6 and Akt (p < 0.05). However, the administration of leucine had no further effect on the phosphorylation of S6 or Akt in the ischemic-reperfused cortex. This study suggests that an acute increase in leucine levels in the brain during early ischemia-reperfusion within a few hours of stroke may offer neuroprotection, possibly due to reduced BBB disruption being one of the major contributing factors. Leucine did not further increase the already elevated phosphorylation of S6 or Akt by ischemia-reperfusion under the current experimental conditions. Our data warrant further studies on the effects of leucine on neuronal survival and its mechanisms in the later stages of cerebral ischemia-reperfusion. |
format | Online Article Text |
id | pubmed-10605042 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106050422023-10-28 Leucine Reduced Blood–Brain Barrier Disruption and Infarct Size in Early Cerebral Ischemia-Reperfusion Chi, Oak Z. Liu, Xia Magsino, Jedrick Weiss, Harvey R. Brain Sci Article A disruption of the blood–brain barrier (BBB) is a crucial pathophysiological change that can impact the outcome of a stroke. Ribosomal protein S6 (S6) and protein kinase B (Akt) play significant roles in early cerebral ischemia-reperfusion injury. Studies have suggested that branched-chain amino acids (BCAAs) may have neuroprotective properties for spinal cord or brain injuries. Therefore, we conducted research to investigate if leucine, one of the BCAAs, could offer neuroprotection and alter BBB disruption, along with its effects on the phosphorylation of S6 and Akt during the early phase of cerebral ischemia-reperfusion, specifically within the thrombolytic therapy time window. In rats, ten min after left middle cerebral artery occlusion (MCAO), 5 µL of 20 mM L-leucine or normal saline was injected into the left lateral ventricle. After two hours of reperfusion following one hour of MCAO, we determined the transfer coefficient (K(i)) of (14)C-α-aminoisobutyric acid to assess the BBB disruption, infarct size, and phosphorylation of S6 and Akt. Ischemia-reperfusion increased the K(i) (+143%, p < 0.001) and the intra-cerebroventricular injection of leucine lowered the K(i) in the ischemic-reperfused cortex (−34%, p < 0.001). Leucine reduced the percentage of cortical infarct (−42%, p < 0.0001) out of the total cortical area. Ischemia-reperfusion alone significantly increased the phosphorylation of both S6 and Akt (p < 0.05). However, the administration of leucine had no further effect on the phosphorylation of S6 or Akt in the ischemic-reperfused cortex. This study suggests that an acute increase in leucine levels in the brain during early ischemia-reperfusion within a few hours of stroke may offer neuroprotection, possibly due to reduced BBB disruption being one of the major contributing factors. Leucine did not further increase the already elevated phosphorylation of S6 or Akt by ischemia-reperfusion under the current experimental conditions. Our data warrant further studies on the effects of leucine on neuronal survival and its mechanisms in the later stages of cerebral ischemia-reperfusion. MDPI 2023-09-26 /pmc/articles/PMC10605042/ /pubmed/37891741 http://dx.doi.org/10.3390/brainsci13101372 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Chi, Oak Z. Liu, Xia Magsino, Jedrick Weiss, Harvey R. Leucine Reduced Blood–Brain Barrier Disruption and Infarct Size in Early Cerebral Ischemia-Reperfusion |
title | Leucine Reduced Blood–Brain Barrier Disruption and Infarct Size in Early Cerebral Ischemia-Reperfusion |
title_full | Leucine Reduced Blood–Brain Barrier Disruption and Infarct Size in Early Cerebral Ischemia-Reperfusion |
title_fullStr | Leucine Reduced Blood–Brain Barrier Disruption and Infarct Size in Early Cerebral Ischemia-Reperfusion |
title_full_unstemmed | Leucine Reduced Blood–Brain Barrier Disruption and Infarct Size in Early Cerebral Ischemia-Reperfusion |
title_short | Leucine Reduced Blood–Brain Barrier Disruption and Infarct Size in Early Cerebral Ischemia-Reperfusion |
title_sort | leucine reduced blood–brain barrier disruption and infarct size in early cerebral ischemia-reperfusion |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10605042/ https://www.ncbi.nlm.nih.gov/pubmed/37891741 http://dx.doi.org/10.3390/brainsci13101372 |
work_keys_str_mv | AT chioakz leucinereducedbloodbrainbarrierdisruptionandinfarctsizeinearlycerebralischemiareperfusion AT liuxia leucinereducedbloodbrainbarrierdisruptionandinfarctsizeinearlycerebralischemiareperfusion AT magsinojedrick leucinereducedbloodbrainbarrierdisruptionandinfarctsizeinearlycerebralischemiareperfusion AT weissharveyr leucinereducedbloodbrainbarrierdisruptionandinfarctsizeinearlycerebralischemiareperfusion |