There are no known medications or medication combinations that significantly aid in the recovery of damaged axons in the central nervous system. Using the rat optic nerve crush model, we employed systems pharmacology techniques to analyse the pathways underpinning axonal growth and discover a four-drug combination that controls numerous intracellular processes in the cell body and axon. To encourage retinal ganglion cells to generate axons, we intravitreally administered the agonists HU-210 (cannabinoid receptor-1) and IL-6 (interleukin 6 receptor). Since computer simulations indicated that this pharmacological combination regulating two subcellular processes at the growth cone generates synergistic growth, we used Taxol to stabilise developing microtubules and activated protein C to remove the debris field in gel foam at the site of nerve injury. Adult CNS damage is frequently irreversible. Two main variables, including myelin-associated chemicals, which limit axonal development, as well as improper activation of intracellular signalling pathways, are the main reasons of this incapacity. The MTOR and STAT3 pathways are two of these. Axonal regeneration was triggered by simultaneous genome-level activation of several pathways, and it was strong and long-lasting. Similar to this, prolonged regeneration of optic nerve fibres to the brain results from sustained activation of the MTOR pathway by genetic manipulation in conjunction with visual stimulation. Following peripheral nerve injury, transcriptomic investigations of dorsal root ganglion neurons have revealed the participation of various signalling pathways, including neurotrophins, TGF cytokine, and JAK-STAT. The field of axon regeneration has been looking for the processes underpinning peripheral axon regeneration for the past 30 years. This method has given rise to the hypothesis that, in a suitable environment, CNS neurons could renew their axons. The CNS is not, however, a setting that supports axon regeneration. The glial scar, which contains many inhibitory molecules and released proteins that hinder axon regeneration, is created as a result of CNS injury. Other components, including as semaphorins and myelin associated glycoproteins, which are produced in healthy tissue, operate as obstacles to regeneration in addition to the glial scar. These inhibiting substances bind to receptors found on expanding neurites, signalling the collapse of the growth cone and the end of axon renewal. The ability of serotonin axons from the dorsal/median raphe and norepinephrine axons from the locus coeruleus into the cerebral cortex to regenerate axons after injury demonstrates that adult mammalian CNS neurons are indeed capable of doing so through an environment that has historically been thought to be impermissive. Axons from serotonin and norepinephrine-expressing neurons have been seen to recover over extended distances after traumatic brain injury, a cortical stab wound, or specific chemical insults by a number of research teams. Determine whether serotonin and norepinephrine neurons experience a similar reversion process by comparing the transcriptome of regenerating neuromodulatory neurons to those of DRG and CST neurons at comparable timepoints. The outcomes of these studies may alter how we approach the quest for treatments for traumatic brain and spinal cord injuries. It is more effective to focus on preserving a "redevelopment" phenotype particular to CNS neurons or perhaps a programme specific to nerumodulatory neurons rather than trying to stimulate expression of the optimum transcriptional programmes associated with peripheral nerve regeneration.

Damon Henderson