Published Online
on March 3, 2005

A more recent version of this article appeared on April 1, 2005

This Article Full Text (PDF) All Versions of this Article: 36/4/847    most recent 01.STR.0000158923.19956.73v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhang, L. Articles by Chopp, M. Search for Related Content PubMed PubMed Citation Articles by Zhang, L. Articles by Chopp, M. Related Collections Angiogenesis Embolic stroke

Submitted on September 17, 2004
Revised on December 16, 2004
Accepted on January 14, 2005

Functional Recovery in Aged and Young Rats After Embolic Stroke. Treatment With a Phosphodiesterase Type 5 Inhibitor

Li Zhang MD; Rui Lan Zhang MD; Ying Wang MD; Chunling Zhang BS; Zheng Gang Zhang MD, PhD; He Meng MD, PhD; and Michael Chopp PhD^*

From the Department of Neurology (L.Z., R.L.Z., Y.W., C.Z., Z.Z., H.M., M.C.), Henry Ford Health Sciences Center, Detroit, Mich; and the Department of Physics (M.C.), Oakland University, Rochester, Mich.

^* To whom correspondence should be addressed. E-mail: chopp{at}neuro.hfh.edu.

Background and Purpose--Advanced age is associated with a decrease in brain plasticity compared with the young adult. Sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor promotes brain plasticity and improves functional outcome after stroke in the young animal. Here, we test the hypothesis that sildenafil provides restorative therapeutic benefit to the aged animal.

Methods--Male Wistar rats (aged, 18-month old; young, 3-month old) were subjected to embolic stroke. Saline or sildenafil was administered daily at a dose of 2 mg/kg orally or 10 mg/kg subcutaneously for 7 consecutive days starting 24 hour after stroke onset.

Results--Aged rats exhibited significant impairment of functional recovery and reductions of vascular density, and endothelial cell proliferation compared with young rats. Aged rats treated with sildenafil at a dose of 10 mg/kg but not 2 mg/kg, showed significant improvements of functional recovery and concomitant increases in cortical cyclic guanosine 3',5'-cyclic monophosphate (cGMP) level, vascular density, endothelial cell proliferation, and synaptogenesis compared with aged rats treated with saline. In young rats, treatment with sildenafil at a dose of 2 or 10 mg/kg significantly enhanced functional recovery and amplified brain plasticity compared with young rats treated with saline.

Conclusion--Age is associated with reduction of angiogenesis, and poor neurological functional recovery after stroke. However, treatment of aged stroke rats with sildenafil improves functional recovery that is likely fostered by enhancement of angiogenesis and synaptogenesis.

Key words: angiogenesis • embolism • recovery of function

This article has been cited by other articles:

				F. S. Menniti, J. Ren, T. M. Coskran, J. Liu, D. Morton, D. K. Sietsma, A. Som, D. T. Stephenson, B. A. Tate, and S. P. Finklestein Phosphodiesterase 5A Inhibitors Improve Functional Recovery after Stroke in Rats: Optimized Dosing Regimen with Implications for Mechanism J. Pharmacol. Exp. Ther., December 1, 2009; 331(3): 842 - 850. [Abstract] [Full Text] [PDF]

				A. Caretti, P. Bianciardi, R. Ronchi, M. Fantacci, M. Guazzi, and M. Samaja Phosphodiesterase-5 Inhibition Abolishes Neuron Apoptosis Induced by Chronic Hypoxia Independently of Hypoxia-Inducible Factor-1{alpha} Signaling Experimental Biology and Medicine, October 1, 2008; 233(10): 1222 - 1230. [Abstract] [Full Text] [PDF]

				G. Ding, Q. Jiang, L. Li, L. Zhang, Z. G. Zhang, K. A. Ledbetter, L. Gollapalli, S. Panda, Q. Li, J. R. Ewing, et al. Angiogenesis Detected After Embolic Stroke in Rat Brain Using Magnetic Resonance T2*WI Stroke, May 1, 2008; 39(5): 1563 - 1568. [Abstract] [Full Text] [PDF]

				A. Senthilkumar, R. D. Smith, J. Khitha, N. Arora, S. Veerareddy, W. Langston, J. H. Chidlow Jr, S. C. Barlow, X. Teng, R. P. Patel, et al. Sildenafil Promotes Ischemia-Induced Angiogenesis Through a PKG-Dependent Pathway Arterioscler Thromb Vasc Biol, September 1, 2007; 27(9): 1947 - 1954. [Abstract] [Full Text] [PDF]

				R. L. Zhang, Z. G. Zhang, and M. Chopp Neurogenesis in the Adult Ischemic Brain: Generation, Migration, Survival, and Restorative Therapy Neuroscientist, October 1, 2005; 11(5): 408 - 416. [Abstract] [PDF]