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

Abstract

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. KeywordsNogo-A; Nogo-66 receptor; Small proline-rich repeat protein 1A (SPRR1A); Traumatic brain injury; Oligodendrocytes

Minocycline but not valproic acid influence the density of NogoA-immunoreactive neurons in the hilus of the dentate gyrus of the rats subjected to intracerebral haematoma

“…In human, increased immunoreactivity of NogoA-positive hippocampal neurons was observed in Alzheimer disease [9] and temporal lobe epilepsy [3]. The increase was also present in the experimental models of brain diseases including epilepsy [28,41] or brain injury [26,28,30].…”

“…In the fluid percussion model of traumatic brain injury applied to frontoparietal cortex, numerous NogoA-ir neurons were observed in the hilus of the dentate gyrus of sham-injured rats. These neurons in the ipsilateral HDG were found to be selectively vulnerable to injury and their number was decreased 7 days after injury [26]. Unfortunately, analysis of contralateral hippocampus was performed in this study.…”

Neuronal Nogo-A upregulation does not contribute to ER stress-associated apoptosis but participates in the regenerative response in the axotomized adult retina

“…Here, we found that the neuronal content of Nogo-A was increased in RGC neurons after optic nerve injury, similar to results recently described for cortical and thalamic neurons after stroke. 13,14 This opens the possibility that neuronal Nogo-A may have a role in the cell death/survival and/or regeneration response of injured CNS neurons. 14 Interestingly, the genetic deletion of Nogo-A/B in mutant mice worsened the motor and cognitive deficits after traumatic brain injury and accelerated the degeneration of motorneuron axons in a model of amyotrophic lateral sclerosis (ALS).…”

“…13,14 This opens the possibility that neuronal Nogo-A may have a role in the cell death/survival and/or regeneration response of injured CNS neurons. 14 Interestingly, the genetic deletion of Nogo-A/B in mutant mice worsened the motor and cognitive deficits after traumatic brain injury and accelerated the degeneration of motorneuron axons in a model of amyotrophic lateral sclerosis (ALS). [14][15][16] A neuroprotective effect of Nogo was proposed to be related to an attenuation of endoplasmic reticulum (ER) stress.…”

“…14 Interestingly, the genetic deletion of Nogo-A/B in mutant mice worsened the motor and cognitive deficits after traumatic brain injury and accelerated the degeneration of motorneuron axons in a model of amyotrophic lateral sclerosis (ALS). [14][15][16] A neuroprotective effect of Nogo was proposed to be related to an attenuation of endoplasmic reticulum (ER) stress. 15 Only few and contradictory observations are available on such a role of Nogo (reticulon 4 (RTN4)) or other RTN proteins, and they rely mostly on in vitro or overexpression experiments.…”