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Forebrain ischemia triggers GABAergic system degeneration in substantia nigra at chronic stages in rats.

Lin B, Levy S, Raval AP, Perez-Pinzon MA, Defazio RA - Cardiovasc Psychiatry Neurol (2010)

Bottom Line: At day 56, the optical density of GAD67-, but not VGAT-, immunoreactivity in substantia nigra pars reticulata (SNR)-significantly decreased.CR-neurons concentrated in substantia nigra pars compacta (SNC) were reduced by 27% from day 3 (n = 5) to day 56 (n = 7, ANOVA, p < .01).Our results demonstrate delayed impairment of the GABAergic system components in SN and associated with movement deficits after global ischemia.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology (D4-5), Cerebral Vascular Disease Research Center, University of Miami Miller School of Medicine, P.O. Box 016960, Miami, FL 33101, USA.

ABSTRACT
The long-term consequences of forebrain ischemia include delayed Parkinson's syndrome. This study revealed delayed neurodegeneration in the substantia nigra 8 weeks after 12.5 minutes of global ischemia in rat brain. Following neuronal loss of 30-40% in central and dorsolateral striatum at day 3, neuronal damage in the substantia nigra (SN) was assessed at 4-8 weeks using immunohistochemistry for glutamate decarboxylase 67 (GAD67), vesicular GABA transporter (VGAT), and calretinin (CR). At day 56, the optical density of GAD67-, but not VGAT-, immunoreactivity in substantia nigra pars reticulata (SNR)-significantly decreased. CR-neurons concentrated in substantia nigra pars compacta (SNC) were reduced by 27% from day 3 (n = 5) to day 56 (n = 7, ANOVA, p < .01). Movement coordination was impaired at day 56, as evaluated using beam-walking test (time-to-traverse 5.6 ± 1.2 sec versus 11.8 ± 5.4 sec; sham versus ischemia, p < .05, n = 5, and 7, resp.). Our results demonstrate delayed impairment of the GABAergic system components in SN and associated with movement deficits after global ischemia.

No MeSH data available.


Related in: MedlinePlus

Functional recovery after global ischemia was tested using the beam-walking test (BWT). (a) The mean neurological scores (a score of 6 equals normal behavior) by beam-walking test before and after ischemia at days 1, 2, 7, 14, 28, and 56. The ability of the rats to walk on the beam is decreased during the acute phase after global ischemia but gradually recovers (mean ± SEM; *p < .01, paired two-tailed T-Tests assuming unequal variances). (b) The time for beam traverse before and at day 56 after ischemia. Despite the improvement in the qualitative scoring (i.e., no foot faults), the ischemic rats were much slower than sham or baseline. Because the ischemic rats were not able to complete the traverse until day 56, these are the only time points available. *indicates significant difference between preischemia and postischemia in (a) and the difference between sham and ischemia group at day 56 in (b) (mean ± SEM; p < .02; ischemia day 56 versus either sham or baseline, ANOVA, Tukey HSD post hoc test between all four groups).
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fig9: Functional recovery after global ischemia was tested using the beam-walking test (BWT). (a) The mean neurological scores (a score of 6 equals normal behavior) by beam-walking test before and after ischemia at days 1, 2, 7, 14, 28, and 56. The ability of the rats to walk on the beam is decreased during the acute phase after global ischemia but gradually recovers (mean ± SEM; *p < .01, paired two-tailed T-Tests assuming unequal variances). (b) The time for beam traverse before and at day 56 after ischemia. Despite the improvement in the qualitative scoring (i.e., no foot faults), the ischemic rats were much slower than sham or baseline. Because the ischemic rats were not able to complete the traverse until day 56, these are the only time points available. *indicates significant difference between preischemia and postischemia in (a) and the difference between sham and ischemia group at day 56 in (b) (mean ± SEM; p < .02; ischemia day 56 versus either sham or baseline, ANOVA, Tukey HSD post hoc test between all four groups).

Mentions: After training, the preischemia traversing beam score was 6 for all 30 rats. The traversing score of sham rats reached 6 point (no faults) at 48 hours after surgery while ischemic rats did not reach 6 until day 56. Compared to sham rats, the ischemia rats had significantly lower scores at days 1, 2, and 7 after the insult (see Figure 9(a)). At day 56, the score of ischemia group reached 6; however, the ischemic rats traversed slower than sham rats, and the mean time for traverse was 11.8 ± 5.4 (ischemia, n = 7) versus 5.6 ± 1.2 seconds (sham, n = 5) (Figure 9(b)). Compared to preischemia the rats walked significantly slower at day 56: the traverse time was 4.88 ± 0.92 versus 11.8 ± 5.4 seconds (postischemic group, baseline (day 0 versus day 56; Figure 9(b)). However, sham rats did not traverse slower in day 56 than presurgery (5.16 ± 0.66 versus 5.6 ± 1.2 seconds; sham group, baseline versus day 56). This indicates ischemia rats took more time to finish traverse due to brain injury, not aging or surgery.


Forebrain ischemia triggers GABAergic system degeneration in substantia nigra at chronic stages in rats.

Lin B, Levy S, Raval AP, Perez-Pinzon MA, Defazio RA - Cardiovasc Psychiatry Neurol (2010)

Functional recovery after global ischemia was tested using the beam-walking test (BWT). (a) The mean neurological scores (a score of 6 equals normal behavior) by beam-walking test before and after ischemia at days 1, 2, 7, 14, 28, and 56. The ability of the rats to walk on the beam is decreased during the acute phase after global ischemia but gradually recovers (mean ± SEM; *p < .01, paired two-tailed T-Tests assuming unequal variances). (b) The time for beam traverse before and at day 56 after ischemia. Despite the improvement in the qualitative scoring (i.e., no foot faults), the ischemic rats were much slower than sham or baseline. Because the ischemic rats were not able to complete the traverse until day 56, these are the only time points available. *indicates significant difference between preischemia and postischemia in (a) and the difference between sham and ischemia group at day 56 in (b) (mean ± SEM; p < .02; ischemia day 56 versus either sham or baseline, ANOVA, Tukey HSD post hoc test between all four groups).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2957857&req=5

fig9: Functional recovery after global ischemia was tested using the beam-walking test (BWT). (a) The mean neurological scores (a score of 6 equals normal behavior) by beam-walking test before and after ischemia at days 1, 2, 7, 14, 28, and 56. The ability of the rats to walk on the beam is decreased during the acute phase after global ischemia but gradually recovers (mean ± SEM; *p < .01, paired two-tailed T-Tests assuming unequal variances). (b) The time for beam traverse before and at day 56 after ischemia. Despite the improvement in the qualitative scoring (i.e., no foot faults), the ischemic rats were much slower than sham or baseline. Because the ischemic rats were not able to complete the traverse until day 56, these are the only time points available. *indicates significant difference between preischemia and postischemia in (a) and the difference between sham and ischemia group at day 56 in (b) (mean ± SEM; p < .02; ischemia day 56 versus either sham or baseline, ANOVA, Tukey HSD post hoc test between all four groups).
Mentions: After training, the preischemia traversing beam score was 6 for all 30 rats. The traversing score of sham rats reached 6 point (no faults) at 48 hours after surgery while ischemic rats did not reach 6 until day 56. Compared to sham rats, the ischemia rats had significantly lower scores at days 1, 2, and 7 after the insult (see Figure 9(a)). At day 56, the score of ischemia group reached 6; however, the ischemic rats traversed slower than sham rats, and the mean time for traverse was 11.8 ± 5.4 (ischemia, n = 7) versus 5.6 ± 1.2 seconds (sham, n = 5) (Figure 9(b)). Compared to preischemia the rats walked significantly slower at day 56: the traverse time was 4.88 ± 0.92 versus 11.8 ± 5.4 seconds (postischemic group, baseline (day 0 versus day 56; Figure 9(b)). However, sham rats did not traverse slower in day 56 than presurgery (5.16 ± 0.66 versus 5.6 ± 1.2 seconds; sham group, baseline versus day 56). This indicates ischemia rats took more time to finish traverse due to brain injury, not aging or surgery.

Bottom Line: At day 56, the optical density of GAD67-, but not VGAT-, immunoreactivity in substantia nigra pars reticulata (SNR)-significantly decreased.CR-neurons concentrated in substantia nigra pars compacta (SNC) were reduced by 27% from day 3 (n = 5) to day 56 (n = 7, ANOVA, p < .01).Our results demonstrate delayed impairment of the GABAergic system components in SN and associated with movement deficits after global ischemia.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology (D4-5), Cerebral Vascular Disease Research Center, University of Miami Miller School of Medicine, P.O. Box 016960, Miami, FL 33101, USA.

ABSTRACT
The long-term consequences of forebrain ischemia include delayed Parkinson's syndrome. This study revealed delayed neurodegeneration in the substantia nigra 8 weeks after 12.5 minutes of global ischemia in rat brain. Following neuronal loss of 30-40% in central and dorsolateral striatum at day 3, neuronal damage in the substantia nigra (SN) was assessed at 4-8 weeks using immunohistochemistry for glutamate decarboxylase 67 (GAD67), vesicular GABA transporter (VGAT), and calretinin (CR). At day 56, the optical density of GAD67-, but not VGAT-, immunoreactivity in substantia nigra pars reticulata (SNR)-significantly decreased. CR-neurons concentrated in substantia nigra pars compacta (SNC) were reduced by 27% from day 3 (n = 5) to day 56 (n = 7, ANOVA, p < .01). Movement coordination was impaired at day 56, as evaluated using beam-walking test (time-to-traverse 5.6 ± 1.2 sec versus 11.8 ± 5.4 sec; sham versus ischemia, p < .05, n = 5, and 7, resp.). Our results demonstrate delayed impairment of the GABAergic system components in SN and associated with movement deficits after global ischemia.

No MeSH data available.


Related in: MedlinePlus