Successful Regeneration After Experimental Stroke by Granulocyte-Colony Stimulating Factor Is Not Further Enhanced by Constraint-Induced Movement Therapy Either in Concurrent or in Sequential Combination Therapy

• Published in: Stroke (1970) Vol. 43; no. 1; pp. 185 - 192
• Main Authors: DIEDERICH, Kai, QUENNET, Verena, BAUER, Henrike, MÜLLER, Harald D, WERSCHING, Heike, SCHABITZ, Wolf-Rüdiger, MINNERUP, Jens, SOMMER, Clemens
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 2012
• Subjects: Animals; Biological and medical sciences; Brain - drug effects; Brain - physiology; Brain Ischemia - drug therapy; Brain Ischemia - physiopathology; Brain Ischemia - therapy; Combined Modality Therapy; Granulocyte Colony-Stimulating Factor - pharmacology; Granulocyte Colony-Stimulating Factor - therapeutic use; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Male; Medical sciences; Nervous system (semeiology, syndromes); Neurology; Physical Therapy Modalities; Rats; Rats, Wistar; Recovery of Function - drug effects; Regeneration; Stroke - drug therapy; Stroke - physiopathology; Stroke - therapy; Vascular diseases and vascular malformations of the nervous system; Stroke; Drug combination; Nervous system diseases; Constraint; Granulocyte; Cardiovascular disease; Cerebrospinal fluid; G-CSF; Cerebral disorder; Vascular disease; Autoradiography; Regeneration; CIMT; Central nervous system disease; receptor autoradiography; Combined treatment; FAU; Cerebrovascular disease
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/STROKEAHA.111.622159

Both application of granulocyte-colony stimulating factor (G-CSF) and constraint-induced movement therapy (CIMT) have been shown to improve outcome after experimental stroke. The aim of the present study was to determine whether concurrent or sequential combination of both therapies will further enhance therapeutic benefit and whether specific modifications in the abundance of various neurotransmitter receptors do occur. Adult male Wistar rats were subjected to photothrombotic ischemia and assigned to the following treatment groups (n=20 each): (1) ischemic control (saline); (2) CIMT (CIMT between poststroke Days 2 and 11; (3) G-CSF (10 μg/kg G-CSF daily between poststroke Days 2 and 11; (4) combined concurrent group (CIMT plus 10 μg/kg G-CSF daily between poststroke Days 2 and 11; and (5) combined sequential group (CIMT between poststroke Days 2 and 11 and 10 μg/kg G-CSF daily between poststroke Days 12 and 21, respectively). Rats were functionally tested before and up to 4 weeks after ischemia. Quantitative receptor autography was performed for N-methyl-d-aspartate, AMPA, and GABA(A) receptors. Significant improvement of functional outcome was seen in all groups treated with G-CSF alone and in either combination with CIMT, whereas CIMT alone failed to enhance recovery. Infarct sizes and remaining cortical tissue did not differ in the various treatment groups. Failure of significant benefit in the CIMT group was associated with a shift toward inhibition in perilesional and remote cortical regions. Our findings disclose G-CSF as the major player for enhanced recovery after experimental stroke, preventing a shift toward inhibition as seen in the CIMT group.