HMG-CoA Reductase Inhibition Promotes Neurological Recovery, Peri-Lesional Tissue Remodeling, and Contralesional Pyramidal Tract Plasticity after Focal Cerebral Ischemia

Kilic, Ertugrul; Reitmeir, Raluca; Kilic, Ülkan; Caglayan, Ahmet Burak; Beker, Mustafa Caglar; Kelestemur, Taha; Ethemoglu, Muhsine Sinem; Ozturk, Gurkan; Hermann, Dirk M (2014). HMG-CoA Reductase Inhibition Promotes Neurological Recovery, Peri-Lesional Tissue Remodeling, and Contralesional Pyramidal Tract Plasticity after Focal Cerebral Ischemia. Frontiers in cellular neuroscience, 8, p. 422. Frontiers Research Foundation 10.3389/fncel.2014.00422

[img]
Preview
Text
fncel-08-00422.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (2MB) | Preview

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are widely used for secondary stroke prevention. Besides their lipid-lowering activity, pleiotropic effects on neuronal survival, angiogenesis, and neurogenesis have been described. In view of these observations, we were interested whether HMG-CoA reductase inhibition in the post-acute stroke phase promotes neurological recovery, peri-lesional, and contralesional neuronal plasticity. We examined effects of the HMG-CoA reductase inhibitor rosuvastatin (0.2 or 2.0 mg/kg/day i.c.v.), administered starting 3 days after 30 min of middle cerebral artery occlusion for 30 days. Here, we show that rosuvastatin treatment significantly increased the grip strength and motor coordination of animals, promoted exploration behavior, and reduced anxiety. It was associated with structural remodeling of peri-lesional brain tissue, reflected by increased neuronal survival, enhanced capillary density, and reduced striatal and corpus callosum atrophy. Increased sprouting of contralesional pyramidal tract fibers crossing the midline in order to innervate the ipsilesional red nucleus was noticed in rosuvastatin compared with vehicle-treated mice, as shown by anterograde tract tracing experiments. Western blot analysis revealed that the abundance of HMG-CoA reductase was increased in the contralesional hemisphere at 14 and 28 days post-ischemia. Our data support the idea that HMG-CoA reductase inhibition promotes brain remodeling and plasticity far beyond the acute stroke phase, resulting in neurological recovery.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurosurgery

UniBE Contributor:

Reitmeir, Raluca

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1662-5102

Publisher:

Frontiers Research Foundation

Language:

English

Submitter:

Nicole Söll

Date Deposited:

17 Mar 2015 10:39

Last Modified:

17 Mar 2015 10:39

Publisher DOI:

10.3389/fncel.2014.00422

PubMed ID:

25565957

Uncontrolled Keywords:

middle cerebral artery occlusion, neurological recovery, neuronal plasticity, restorative therapy, statin, tract tracing

BORIS DOI:

10.7892/boris.64568

URI:

https://boris.unibe.ch/id/eprint/64568

Actions (login required)

Edit item Edit item
Provide Feedback