Limits...
Statins Promote Long-Term Recovery after Ischemic Stroke by Reconnecting Noradrenergic Neuronal Circuitry.

Cho KJ, Cheon SY, Kim GW - Neural Plast. (2015)

Bottom Line: Inhibitors of HMG-CoA reductase (statins), widely used to lower cholesterol in coronary heart and vascular disease, are effective drugs in reducing the risk of stroke and improving its outcome in the long term.This study investigated the effects of statins on the recovery of NA neuron circuitry and its function after transient focal cerebral ischemia (tFCI).Statins may be implicated to play facilitating roles in the recovery of the NA neuron and its function.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, College of Medicine, Yonsei University, Seoul 120-752, Republic of Korea.

ABSTRACT
Inhibitors of HMG-CoA reductase (statins), widely used to lower cholesterol in coronary heart and vascular disease, are effective drugs in reducing the risk of stroke and improving its outcome in the long term. After ischemic stroke, cardiac autonomic dysfunction and psychological problems are common complications related to deficits in the noradrenergic (NA) system. This study investigated the effects of statins on the recovery of NA neuron circuitry and its function after transient focal cerebral ischemia (tFCI). Using the wheat germ agglutinin (WGA) transgene technique combined with the recombinant adenoviral vector system, NA-specific neuronal pathways were labeled, and were identified in the locus coeruleus (LC), where NA neurons originate. NA circuitry in the atorvastatin-treated group recovered faster than in the vehicle-treated group. The damaged NA circuitry was partly reorganized with the gradual recovery of autonomic dysfunction and neurobehavioral deficit. Newly proliferated cells might contribute to reorganizing NA neurons and lead anatomic and functional recovery of NA neurons. Statins may be implicated to play facilitating roles in the recovery of the NA neuron and its function.

No MeSH data available.


Related in: MedlinePlus

Physiological recovery and behavioral tests relating to the NA circuitry. (a) Profiles of blood pressure in vehicle-treated or atorvastatin-treated mice after tFCI. (b) Effects of atorvastatin on behavioral parameters in the light/dark test. The light/dark test was performed at 30, 180, and 240 days after tFCI in mice. The effect on mouse behavior in the light/dark test was determined by p-test. Data presented are the mean value ± S.E.M, ∗p < 0.05 relative to the vehicle group. (c) Effects of atorvastatin on behavioral parameters in the aggression-intruder test in mice. Aggression-intruder test was performed at 30, 180, and 240 days after tFCI in mice. The effect on mouse behavior in the aggression-intruder test was determined by p-test. Data presented are mean value ± S.E.M, ∗p < 0.05 relative to the vehicle group.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4581556&req=5

fig5: Physiological recovery and behavioral tests relating to the NA circuitry. (a) Profiles of blood pressure in vehicle-treated or atorvastatin-treated mice after tFCI. (b) Effects of atorvastatin on behavioral parameters in the light/dark test. The light/dark test was performed at 30, 180, and 240 days after tFCI in mice. The effect on mouse behavior in the light/dark test was determined by p-test. Data presented are the mean value ± S.E.M, ∗p < 0.05 relative to the vehicle group. (c) Effects of atorvastatin on behavioral parameters in the aggression-intruder test in mice. Aggression-intruder test was performed at 30, 180, and 240 days after tFCI in mice. The effect on mouse behavior in the aggression-intruder test was determined by p-test. Data presented are mean value ± S.E.M, ∗p < 0.05 relative to the vehicle group.

Mentions: Physiological data and regional cerebral blood flow (rCBF) were measured. There were no statistically significant differences in rCBF during ischemic condition between the group before occlusion and the group after reperfusion (10 min before occlusion, 100 ± 0%; 10 min after occlusion, 23.1 ± 5.3; 10 min after reperfusion, 96.2 ± 3.7; mean ± S.D. of each value; n = 9, each group). Presented in the magnetic resonance images (MRI), the infarcted area after reperfusion from MCAO was gradually reduced, and significantly statin-treated mice showed smaller infarct area than vehicle-treated mice (Figure 3). After a longer period, the damaged brain region was naturally ameliorated even in the vehicle-treated mice, but the recovery showed earlier in statin-treated mice than vehicle-treated mice. The differences in the recovery time determined the behavioral improvement and related to NA neuron circuitry, as shown in the result of the behavior test (Figure 5).


Statins Promote Long-Term Recovery after Ischemic Stroke by Reconnecting Noradrenergic Neuronal Circuitry.

Cho KJ, Cheon SY, Kim GW - Neural Plast. (2015)

Physiological recovery and behavioral tests relating to the NA circuitry. (a) Profiles of blood pressure in vehicle-treated or atorvastatin-treated mice after tFCI. (b) Effects of atorvastatin on behavioral parameters in the light/dark test. The light/dark test was performed at 30, 180, and 240 days after tFCI in mice. The effect on mouse behavior in the light/dark test was determined by p-test. Data presented are the mean value ± S.E.M, ∗p < 0.05 relative to the vehicle group. (c) Effects of atorvastatin on behavioral parameters in the aggression-intruder test in mice. Aggression-intruder test was performed at 30, 180, and 240 days after tFCI in mice. The effect on mouse behavior in the aggression-intruder test was determined by p-test. Data presented are mean value ± S.E.M, ∗p < 0.05 relative to the vehicle group.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4581556&req=5

fig5: Physiological recovery and behavioral tests relating to the NA circuitry. (a) Profiles of blood pressure in vehicle-treated or atorvastatin-treated mice after tFCI. (b) Effects of atorvastatin on behavioral parameters in the light/dark test. The light/dark test was performed at 30, 180, and 240 days after tFCI in mice. The effect on mouse behavior in the light/dark test was determined by p-test. Data presented are the mean value ± S.E.M, ∗p < 0.05 relative to the vehicle group. (c) Effects of atorvastatin on behavioral parameters in the aggression-intruder test in mice. Aggression-intruder test was performed at 30, 180, and 240 days after tFCI in mice. The effect on mouse behavior in the aggression-intruder test was determined by p-test. Data presented are mean value ± S.E.M, ∗p < 0.05 relative to the vehicle group.
Mentions: Physiological data and regional cerebral blood flow (rCBF) were measured. There were no statistically significant differences in rCBF during ischemic condition between the group before occlusion and the group after reperfusion (10 min before occlusion, 100 ± 0%; 10 min after occlusion, 23.1 ± 5.3; 10 min after reperfusion, 96.2 ± 3.7; mean ± S.D. of each value; n = 9, each group). Presented in the magnetic resonance images (MRI), the infarcted area after reperfusion from MCAO was gradually reduced, and significantly statin-treated mice showed smaller infarct area than vehicle-treated mice (Figure 3). After a longer period, the damaged brain region was naturally ameliorated even in the vehicle-treated mice, but the recovery showed earlier in statin-treated mice than vehicle-treated mice. The differences in the recovery time determined the behavioral improvement and related to NA neuron circuitry, as shown in the result of the behavior test (Figure 5).

Bottom Line: Inhibitors of HMG-CoA reductase (statins), widely used to lower cholesterol in coronary heart and vascular disease, are effective drugs in reducing the risk of stroke and improving its outcome in the long term.This study investigated the effects of statins on the recovery of NA neuron circuitry and its function after transient focal cerebral ischemia (tFCI).Statins may be implicated to play facilitating roles in the recovery of the NA neuron and its function.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, College of Medicine, Yonsei University, Seoul 120-752, Republic of Korea.

ABSTRACT
Inhibitors of HMG-CoA reductase (statins), widely used to lower cholesterol in coronary heart and vascular disease, are effective drugs in reducing the risk of stroke and improving its outcome in the long term. After ischemic stroke, cardiac autonomic dysfunction and psychological problems are common complications related to deficits in the noradrenergic (NA) system. This study investigated the effects of statins on the recovery of NA neuron circuitry and its function after transient focal cerebral ischemia (tFCI). Using the wheat germ agglutinin (WGA) transgene technique combined with the recombinant adenoviral vector system, NA-specific neuronal pathways were labeled, and were identified in the locus coeruleus (LC), where NA neurons originate. NA circuitry in the atorvastatin-treated group recovered faster than in the vehicle-treated group. The damaged NA circuitry was partly reorganized with the gradual recovery of autonomic dysfunction and neurobehavioral deficit. Newly proliferated cells might contribute to reorganizing NA neurons and lead anatomic and functional recovery of NA neurons. Statins may be implicated to play facilitating roles in the recovery of the NA neuron and its function.

No MeSH data available.


Related in: MedlinePlus