Selective temporal and regional alterations of Nogo-A and small proline-rich repeat protein 1A (SPRR1A) but not Nogo-66 receptor (NgR) occur following traumatic brain injury in the rat.
Axons show a poor regenerative capacity following traumatic central nervous system (CNS) injury, partly due to the expression of inhibitors of axonal outgrowth, of which Nogo-A is considered the most important. We evaluated the acute expression of Nogo-A, the Nogo-66 receptor (NgR) and the novel small proline-rich repeat protein 1A (SPRR1A, previously undetected in brain), following experimental lateral fluid percussion (FP) brain injury in rats. Immunofluorescence with antibodies against Nogo-A, NgR and SPRR1A was combined with antibodies against the neuronal markers NeuN and microtubule-associated protein (MAP)-2 and the oligodendrocyte marker RIP, while Western blot analysis was performed for Nogo-A and NgR. Brain injury produced a significant increase in Nogo-A expression in injured cortex, ipsilateral external capsule and reticular thalamus from days 1-7 post-injury (P < 0.05) compared to controls. Increased expression of Nogo-A was observed in both RIP- and NeuN positive (+) cells in the ipsilateral cortex, in NeuN (+) cells in the CA3 region of the hippocampus and reticular thalamus and in RIP (+) cells in white matter tracts. Alterations in NgR expression were not observed following traumatic brain injury (TBI). Brain injury increased the extent of SPRR1A expression in the ipsilateral cortex and the CA3 at all post-injury time-points in NeuN (+) cells. The marked increases in Nogo-A and SPRR1A in several important brain regions suggest that although inhibitors of axonal growth may be upregulated, the injured brain is also capable of expressing proteins promoting axonal outgrowth following TBI.
Marklund
Niklas
N
Traumatic Brain Injury Laboratory, Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. niklas.marklund@neurokir.uu.se
Fulp
Carl T
CT
Shimizu
Saori
S
Puri
Rishi
R
McMillan
Asenia
A
Strittmatter
Stephen M
SM
McIntosh
Tracy K
TK
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D055233:Cornified Envelope Proline-Rich Proteins; D003720:Densitometry; D007839:Functional Laterality / Q000502:physiology; D058851:GPI-Linked Proteins; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009185:Myelin Proteins / Q000235:genetics*; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D009836:Oligodendroglia / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000235:genetics*; D013788:Thalamus / Q000378:metabolism / Q000473:pathology
D055233:Cornified Envelope Proline-Rich Proteins; D058851:GPI-Linked Proteins; C489787:MAP2 protein, rat; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009185:Myelin Proteins; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface; C000603197:Rtn4 protein, rat; C486581:Rtn4r protein, rat