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

Neurogenesis after ischemic injury in normal and vehicle- or atorvastatin-treated group. (a) Cell proliferation in SVZ of the ischemic hemisphere is identified by BrdU (green) and NeuN (red) immunoreactivity. Many BrdU-positive cells are shown in the SVZ of both groups, with increased BrdU-positive cells in the striatum of the atorvastatin-treated group. (b) A quantitative graph representing the number of BrdU-positive cells, which is increased in the atorvastatin-treated group compared with the vehicle-treated group in the SVZ. (c) The migration of the proliferated cells is identified in the cortex and striatum each stained with BrdU (green) and NeuN (red). Scale bars = 20 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4581556&req=5

fig4: Neurogenesis after ischemic injury in normal and vehicle- or atorvastatin-treated group. (a) Cell proliferation in SVZ of the ischemic hemisphere is identified by BrdU (green) and NeuN (red) immunoreactivity. Many BrdU-positive cells are shown in the SVZ of both groups, with increased BrdU-positive cells in the striatum of the atorvastatin-treated group. (b) A quantitative graph representing the number of BrdU-positive cells, which is increased in the atorvastatin-treated group compared with the vehicle-treated group in the SVZ. (c) The migration of the proliferated cells is identified in the cortex and striatum each stained with BrdU (green) and NeuN (red). Scale bars = 20 μm.

Mentions: In postischemic brain injury, neuronal cells derived from neural precursor cells are newly born and the cells can be detected by bromodeoxyuridine (BrdU). The BrdU-immunopositive cells were observed in the postischemic cortex, striatum, and subventricular zone (SVZ) on the ipsilateral side of the ischemic infarct at 1 month and 6 months (Figures 4(a) and 4(b)). The BrdU-positive cells were more frequently observed in the ipsilateral side of the statin-treated mice than in the contralateral side. Especially at 1 month after tFCI, many BrdU- and NeuN-immunopositive cells were detected in the lesioned cortex and striatum at the direct site to ischemic damage by MCAO (Figure 4(c)). It could be implicated that newborn cells have arisen from the SVZ and migrated into striatum and even into cortical area. Moreover, the proliferation of neural cells is promoted by long-term statin treatment. At 6 months and 8 months after fFCI, the incidence of BrdU-positive cells in the ipsilateral striatum and cortex was significantly diminished compared to that of 1 month after fFCI (data not shown). The BrdU-positive cells were not detected in either striatum or cortex, but a few BrdU-positive cells were detected in SVZ and corpus callosum.


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

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

Neurogenesis after ischemic injury in normal and vehicle- or atorvastatin-treated group. (a) Cell proliferation in SVZ of the ischemic hemisphere is identified by BrdU (green) and NeuN (red) immunoreactivity. Many BrdU-positive cells are shown in the SVZ of both groups, with increased BrdU-positive cells in the striatum of the atorvastatin-treated group. (b) A quantitative graph representing the number of BrdU-positive cells, which is increased in the atorvastatin-treated group compared with the vehicle-treated group in the SVZ. (c) The migration of the proliferated cells is identified in the cortex and striatum each stained with BrdU (green) and NeuN (red). Scale bars = 20 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: Neurogenesis after ischemic injury in normal and vehicle- or atorvastatin-treated group. (a) Cell proliferation in SVZ of the ischemic hemisphere is identified by BrdU (green) and NeuN (red) immunoreactivity. Many BrdU-positive cells are shown in the SVZ of both groups, with increased BrdU-positive cells in the striatum of the atorvastatin-treated group. (b) A quantitative graph representing the number of BrdU-positive cells, which is increased in the atorvastatin-treated group compared with the vehicle-treated group in the SVZ. (c) The migration of the proliferated cells is identified in the cortex and striatum each stained with BrdU (green) and NeuN (red). Scale bars = 20 μm.
Mentions: In postischemic brain injury, neuronal cells derived from neural precursor cells are newly born and the cells can be detected by bromodeoxyuridine (BrdU). The BrdU-immunopositive cells were observed in the postischemic cortex, striatum, and subventricular zone (SVZ) on the ipsilateral side of the ischemic infarct at 1 month and 6 months (Figures 4(a) and 4(b)). The BrdU-positive cells were more frequently observed in the ipsilateral side of the statin-treated mice than in the contralateral side. Especially at 1 month after tFCI, many BrdU- and NeuN-immunopositive cells were detected in the lesioned cortex and striatum at the direct site to ischemic damage by MCAO (Figure 4(c)). It could be implicated that newborn cells have arisen from the SVZ and migrated into striatum and even into cortical area. Moreover, the proliferation of neural cells is promoted by long-term statin treatment. At 6 months and 8 months after fFCI, the incidence of BrdU-positive cells in the ipsilateral striatum and cortex was significantly diminished compared to that of 1 month after fFCI (data not shown). The BrdU-positive cells were not detected in either striatum or cortex, but a few BrdU-positive cells were detected in SVZ and corpus callosum.

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