Limits...
Forced exercise enhances functional recovery after focal cerebral ischemia in spontaneously hypertensive rats.

Park S, Shin J, Hong Y, Kim S, Lee S, Park K, Lkhagvasuren T, Lee SR, Chang KT, Hong Y - Brain Sci (2012)

Bottom Line: Expression of caveolins was decreased in MCAo brain tissue, whereas the levels of iNOS and glial fibrillary acidic protein (GFAP) increased.Additionally, LC3-II and beclin-1 levels were elevated in the MCAo groups.These results suggest that forced exercise may be beneficial for promoting functional recovery following cerebral ischemia through caveolin-dependent mechanisms or interactions between caveolins and these signaling molecules in ischemic brain regions.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular & Metabolic Disease Center, College of Biomedical Science & Engineering, Inje University, Gimhae 621-749, Korea. charm-soo@hanmail.net.

ABSTRACT
Caveolin is the principal protein of caveolae and has been implicated in the pathogenesis of cerebral ischemia. To investigate whether changed expression of caveolins has a pivotal role in focal cerebral ischemia, we induced middle cerebral artery occlusion (MCAo)-reperfusion and examined expression of caveolins, inflammatory activation markers, and mediators of autophagic cell death. We also treated MCAo rats with forced exercise to determine its effects on neurological outcome. Particularly, spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were used to compare the effects of hypertension on focal cerebral ischemia. All MCAo groups showed neurological deficiencies, motor dysfunction, and disruption of balancing ability; however, these pathological changes were more severe in SHR than WKY rats. Expression of caveolins was decreased in MCAo brain tissue, whereas the levels of iNOS and glial fibrillary acidic protein (GFAP) increased. Additionally, LC3-II and beclin-1 levels were elevated in the MCAo groups. Forced exercise attenuated both molecular and behavioral changes in MCAo animals, but SHR rats showed delayed functional recovery and residual molecular changes when compared to WKY rats. These results suggest that forced exercise may be beneficial for promoting functional recovery following cerebral ischemia through caveolin-dependent mechanisms or interactions between caveolins and these signaling molecules in ischemic brain regions.

No MeSH data available.


Related in: MedlinePlus

Altered expression of caveolins and NOS isoforms in WKY and SHR rats after MCAo surgery. (A) Electrophoresis of caveolin-1, -2, -3, nNOS, and iNOS in brain tissue of WKY rats and (B) SHR rats with MCAo surgery. (C) Expression of caveolin-1 mRNA in the MCAo group was significantly decreased compared with that in the sham group in WKY and SHR rats. Also, caveolin-1 mRNA was increased in SHR rats after the treadmill exercise. (D) Caveolin-2 mRNA levels were increased in the MCAo + Ex group in WKY rats after exercise. (E) Caveolin-3 mRNA was decreased in the MCAo group in WKY rats, and it increased after exercise. (F) Expression of iNOS mRNA was increased in the MCAo group of WKY and SHR rats. (G) Expression of nNOS mRNA in the MCAo groups of WKY and SHR rats was decreased. Data shown are means ± SEM. ** p < 0.01, compared with sham group; # p < 0.05, ## p < 0.01 compared with MCAo group; a p < 0.01 between MCAo + Ex WKY and SHR groups; b p < 0.01 between WKY and SHR MCAo groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4061815&req=5

brainsci-02-00483-f004: Altered expression of caveolins and NOS isoforms in WKY and SHR rats after MCAo surgery. (A) Electrophoresis of caveolin-1, -2, -3, nNOS, and iNOS in brain tissue of WKY rats and (B) SHR rats with MCAo surgery. (C) Expression of caveolin-1 mRNA in the MCAo group was significantly decreased compared with that in the sham group in WKY and SHR rats. Also, caveolin-1 mRNA was increased in SHR rats after the treadmill exercise. (D) Caveolin-2 mRNA levels were increased in the MCAo + Ex group in WKY rats after exercise. (E) Caveolin-3 mRNA was decreased in the MCAo group in WKY rats, and it increased after exercise. (F) Expression of iNOS mRNA was increased in the MCAo group of WKY and SHR rats. (G) Expression of nNOS mRNA in the MCAo groups of WKY and SHR rats was decreased. Data shown are means ± SEM. ** p < 0.01, compared with sham group; # p < 0.05, ## p < 0.01 compared with MCAo group; a p < 0.01 between MCAo + Ex WKY and SHR groups; b p < 0.01 between WKY and SHR MCAo groups.

Mentions: RT-PCR analysis was performed to investigate alterations in caveolin and NOS isoforms and to evaluate the effect of forced exercise in WKY and SHR rats after MCAo surgery. Forced treadmill exercise (20–25 m/s, 30 min, twice daily) began 3 days post-injury and lasted for 4 weeks, after which the assessments were performed (i.e., 4 weeks after injury). The caveolin-1, -2, and -3, iNOS, and nNOS mRNA levels were analyzed in core ischemic brain areas of WKY and SHR rats (see Figure 4A,B). The MCAo groups had dramatically down-regulated caveolin-1 mRNA levels in core areas compared to the WKY and SHR Sham groups (p < 0.01). After forced exercise, the caveolin-1 mRNA level increased significantly in WKY and SHR MCAo + Ex groups (p < 0.01). However, the caveolin-1 mRNA level in the SHR MCAo + Ex group was significantly lower than that in the WKY MCAo + Ex group (see Figure 4C; p < 0.05). The caveolin-2 mRNA level decreased in the MCAo groups compared with Sham groups in both WKY and SHR rats (p < 0.05). The caveolin-2 mRNA level was significantly increased only in the WKY MCAo + Ex group (p < 0.01), but not in SHR rats. Additionally, the caveolin-2 mRNA level in the SHR MCAo + Ex group was significantly lower than that in the WKY MCAo + Ex group (p < 0.05; see Figure 4D). MCAo surgery led to reduced caveolin-3 mRNA expression in both WKY (p < 0.05) and SHR rats (p < 0.01). Caveolin-3 was increased in the SHR MCAo + Ex group (p < 0.05). Caveolin-3 mRNA was predominantly expressed in the brain tissue of all groups compared with caveolin-1 and -2 (see Figure 4E). These results indicate that forced exercise has beneficial effects on caveolin expression in MCAo rats, whereas hypertension may have negative effects on recovery of caveolin expression in MCAo rats, particularly the caveolin-1 and -2 isoforms. NO produced by activated iNOS stimulates neuronal apoptotic cell death; therefore, we confirmed iNOS expression in WKY and SHR rats after MCAo surgery. Both WKY and SHR MCAo groups had significant increases in iNOS mRNA levels (p < 0.01). The iNOS mRNA level in the SHR MCAo group was up-regulated compared to the WKY MCAo group (p < 0.05). Forced exercise diminished the iNOS mRNA level in both WKY and SHR rats (p < 0.01); however, despite this change, iNOS mRNA level in the SHR MCAo + Ex group was higher than that in the WKY MCAo + Ex group (see Figure 4F; p < 0.05). These results suggest that hypertension may exacerbate iNOS expression in focal cerebral ischemia. nNOS mRNA levels in both MCAo groups were not significantly different compared with the Sham groups. The nNOS mRNA levels in both MCAo + Ex groups were slightly increased, but these changes were not significant (see Figure 4G).


Forced exercise enhances functional recovery after focal cerebral ischemia in spontaneously hypertensive rats.

Park S, Shin J, Hong Y, Kim S, Lee S, Park K, Lkhagvasuren T, Lee SR, Chang KT, Hong Y - Brain Sci (2012)

Altered expression of caveolins and NOS isoforms in WKY and SHR rats after MCAo surgery. (A) Electrophoresis of caveolin-1, -2, -3, nNOS, and iNOS in brain tissue of WKY rats and (B) SHR rats with MCAo surgery. (C) Expression of caveolin-1 mRNA in the MCAo group was significantly decreased compared with that in the sham group in WKY and SHR rats. Also, caveolin-1 mRNA was increased in SHR rats after the treadmill exercise. (D) Caveolin-2 mRNA levels were increased in the MCAo + Ex group in WKY rats after exercise. (E) Caveolin-3 mRNA was decreased in the MCAo group in WKY rats, and it increased after exercise. (F) Expression of iNOS mRNA was increased in the MCAo group of WKY and SHR rats. (G) Expression of nNOS mRNA in the MCAo groups of WKY and SHR rats was decreased. Data shown are means ± SEM. ** p < 0.01, compared with sham group; # p < 0.05, ## p < 0.01 compared with MCAo group; a p < 0.01 between MCAo + Ex WKY and SHR groups; b p < 0.01 between WKY and SHR MCAo groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061815&req=5

brainsci-02-00483-f004: Altered expression of caveolins and NOS isoforms in WKY and SHR rats after MCAo surgery. (A) Electrophoresis of caveolin-1, -2, -3, nNOS, and iNOS in brain tissue of WKY rats and (B) SHR rats with MCAo surgery. (C) Expression of caveolin-1 mRNA in the MCAo group was significantly decreased compared with that in the sham group in WKY and SHR rats. Also, caveolin-1 mRNA was increased in SHR rats after the treadmill exercise. (D) Caveolin-2 mRNA levels were increased in the MCAo + Ex group in WKY rats after exercise. (E) Caveolin-3 mRNA was decreased in the MCAo group in WKY rats, and it increased after exercise. (F) Expression of iNOS mRNA was increased in the MCAo group of WKY and SHR rats. (G) Expression of nNOS mRNA in the MCAo groups of WKY and SHR rats was decreased. Data shown are means ± SEM. ** p < 0.01, compared with sham group; # p < 0.05, ## p < 0.01 compared with MCAo group; a p < 0.01 between MCAo + Ex WKY and SHR groups; b p < 0.01 between WKY and SHR MCAo groups.
Mentions: RT-PCR analysis was performed to investigate alterations in caveolin and NOS isoforms and to evaluate the effect of forced exercise in WKY and SHR rats after MCAo surgery. Forced treadmill exercise (20–25 m/s, 30 min, twice daily) began 3 days post-injury and lasted for 4 weeks, after which the assessments were performed (i.e., 4 weeks after injury). The caveolin-1, -2, and -3, iNOS, and nNOS mRNA levels were analyzed in core ischemic brain areas of WKY and SHR rats (see Figure 4A,B). The MCAo groups had dramatically down-regulated caveolin-1 mRNA levels in core areas compared to the WKY and SHR Sham groups (p < 0.01). After forced exercise, the caveolin-1 mRNA level increased significantly in WKY and SHR MCAo + Ex groups (p < 0.01). However, the caveolin-1 mRNA level in the SHR MCAo + Ex group was significantly lower than that in the WKY MCAo + Ex group (see Figure 4C; p < 0.05). The caveolin-2 mRNA level decreased in the MCAo groups compared with Sham groups in both WKY and SHR rats (p < 0.05). The caveolin-2 mRNA level was significantly increased only in the WKY MCAo + Ex group (p < 0.01), but not in SHR rats. Additionally, the caveolin-2 mRNA level in the SHR MCAo + Ex group was significantly lower than that in the WKY MCAo + Ex group (p < 0.05; see Figure 4D). MCAo surgery led to reduced caveolin-3 mRNA expression in both WKY (p < 0.05) and SHR rats (p < 0.01). Caveolin-3 was increased in the SHR MCAo + Ex group (p < 0.05). Caveolin-3 mRNA was predominantly expressed in the brain tissue of all groups compared with caveolin-1 and -2 (see Figure 4E). These results indicate that forced exercise has beneficial effects on caveolin expression in MCAo rats, whereas hypertension may have negative effects on recovery of caveolin expression in MCAo rats, particularly the caveolin-1 and -2 isoforms. NO produced by activated iNOS stimulates neuronal apoptotic cell death; therefore, we confirmed iNOS expression in WKY and SHR rats after MCAo surgery. Both WKY and SHR MCAo groups had significant increases in iNOS mRNA levels (p < 0.01). The iNOS mRNA level in the SHR MCAo group was up-regulated compared to the WKY MCAo group (p < 0.05). Forced exercise diminished the iNOS mRNA level in both WKY and SHR rats (p < 0.01); however, despite this change, iNOS mRNA level in the SHR MCAo + Ex group was higher than that in the WKY MCAo + Ex group (see Figure 4F; p < 0.05). These results suggest that hypertension may exacerbate iNOS expression in focal cerebral ischemia. nNOS mRNA levels in both MCAo groups were not significantly different compared with the Sham groups. The nNOS mRNA levels in both MCAo + Ex groups were slightly increased, but these changes were not significant (see Figure 4G).

Bottom Line: Expression of caveolins was decreased in MCAo brain tissue, whereas the levels of iNOS and glial fibrillary acidic protein (GFAP) increased.Additionally, LC3-II and beclin-1 levels were elevated in the MCAo groups.These results suggest that forced exercise may be beneficial for promoting functional recovery following cerebral ischemia through caveolin-dependent mechanisms or interactions between caveolins and these signaling molecules in ischemic brain regions.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular &amp; Metabolic Disease Center, College of Biomedical Science &amp; Engineering, Inje University, Gimhae 621-749, Korea. charm-soo@hanmail.net.

ABSTRACT
Caveolin is the principal protein of caveolae and has been implicated in the pathogenesis of cerebral ischemia. To investigate whether changed expression of caveolins has a pivotal role in focal cerebral ischemia, we induced middle cerebral artery occlusion (MCAo)-reperfusion and examined expression of caveolins, inflammatory activation markers, and mediators of autophagic cell death. We also treated MCAo rats with forced exercise to determine its effects on neurological outcome. Particularly, spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were used to compare the effects of hypertension on focal cerebral ischemia. All MCAo groups showed neurological deficiencies, motor dysfunction, and disruption of balancing ability; however, these pathological changes were more severe in SHR than WKY rats. Expression of caveolins was decreased in MCAo brain tissue, whereas the levels of iNOS and glial fibrillary acidic protein (GFAP) increased. Additionally, LC3-II and beclin-1 levels were elevated in the MCAo groups. Forced exercise attenuated both molecular and behavioral changes in MCAo animals, but SHR rats showed delayed functional recovery and residual molecular changes when compared to WKY rats. These results suggest that forced exercise may be beneficial for promoting functional recovery following cerebral ischemia through caveolin-dependent mechanisms or interactions between caveolins and these signaling molecules in ischemic brain regions.

No MeSH data available.


Related in: MedlinePlus