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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

Expression of WGA and GFP in LC, detecting PRS-WGA adenovirus. (a) Schematic diagram representing the structure of the transgene. (b) WGA immunoreactivity in the noninjured mouse brain. After 2 days of PRS-WGA adenovirus injection in the LC, LC-originated WGA protein was detected in NA neurons and other areas. Scale bars = 500 μm.
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fig1: Expression of WGA and GFP in LC, detecting PRS-WGA adenovirus. (a) Schematic diagram representing the structure of the transgene. (b) WGA immunoreactivity in the noninjured mouse brain. After 2 days of PRS-WGA adenovirus injection in the LC, LC-originated WGA protein was detected in NA neurons and other areas. Scale bars = 500 μm.

Mentions: Adenoviral construct used in this study contains the wheat germ agglutinin (WGA) gene under control of the eight copies of PRS promoter and the green fluorescent protein (GFP) gene under the control of the cytomegalovirus (CMV) promoter, which makes it possible to detect viral delivery to the target sites (Figure 1(a)). After injection of the PRS-WGA adenovirus to the LC, localization of GFP expression and WGA protein was examined on adjacent coronal sections. Colocalization of GFP and WGA demonstrates that WGA protein was synthesized in NA neurons of the LC in our previous report [21]. In sagittal sections of noninjured brain, intense WGA immunoreactivity was detected in the pontine reticular nucleus, motor and sensory trigeminal nucleus, thalamic nucleus, lateral hypothalamic area, deep mesencephalic nucleus, superior colliculus, caudate putamen, corpus callosum, anterior commissure, and olfactory bulb (Figure 1(b)). WGA immunoreactivity was also observed in the parabrachial nucleus, A5 NA cells, substantia nigra, lateral habenular nucleus, hippocampus, optic tract, and piriform cortex in coronal sections (Figure 1(b)). In adenovirus infected mice there was no evidence of cell loss or tissue damage due to the viral infection in LC. All of the experimental animals that recovered after the infection remained healthy until being sacrificed without exhibiting any behavioral abnormalities.


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

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

Expression of WGA and GFP in LC, detecting PRS-WGA adenovirus. (a) Schematic diagram representing the structure of the transgene. (b) WGA immunoreactivity in the noninjured mouse brain. After 2 days of PRS-WGA adenovirus injection in the LC, LC-originated WGA protein was detected in NA neurons and other areas. Scale bars = 500 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Expression of WGA and GFP in LC, detecting PRS-WGA adenovirus. (a) Schematic diagram representing the structure of the transgene. (b) WGA immunoreactivity in the noninjured mouse brain. After 2 days of PRS-WGA adenovirus injection in the LC, LC-originated WGA protein was detected in NA neurons and other areas. Scale bars = 500 μm.
Mentions: Adenoviral construct used in this study contains the wheat germ agglutinin (WGA) gene under control of the eight copies of PRS promoter and the green fluorescent protein (GFP) gene under the control of the cytomegalovirus (CMV) promoter, which makes it possible to detect viral delivery to the target sites (Figure 1(a)). After injection of the PRS-WGA adenovirus to the LC, localization of GFP expression and WGA protein was examined on adjacent coronal sections. Colocalization of GFP and WGA demonstrates that WGA protein was synthesized in NA neurons of the LC in our previous report [21]. In sagittal sections of noninjured brain, intense WGA immunoreactivity was detected in the pontine reticular nucleus, motor and sensory trigeminal nucleus, thalamic nucleus, lateral hypothalamic area, deep mesencephalic nucleus, superior colliculus, caudate putamen, corpus callosum, anterior commissure, and olfactory bulb (Figure 1(b)). WGA immunoreactivity was also observed in the parabrachial nucleus, A5 NA cells, substantia nigra, lateral habenular nucleus, hippocampus, optic tract, and piriform cortex in coronal sections (Figure 1(b)). In adenovirus infected mice there was no evidence of cell loss or tissue damage due to the viral infection in LC. All of the experimental animals that recovered after the infection remained healthy until being sacrificed without exhibiting any behavioral abnormalities.

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