Towards a roadmap in brain protection and recovery

Abstract

This article briefly reviews some of the mechanisms involved in the pathogenesis of neurological diseases, i.e. damage mechanisms (DM), and their interactions and overlap with protection and reparatory processes (i.e. endogenous defence activities). A relationship between DM and endogenous defence activity (EDA) regarding therapy principles will also be described. Currently, it is difficult to find the correct therapeutic approach for brain protection and recovery, especially because we do not fully understand all of the endogenous neurobiological processes, the complete nature of the pathophysiological mechanisms and the links between these two categories. Moreover, we continue to use a simplistic and reductionist approach in this respect. Endogenous neurobiological processes, such as neurotrophicity, neuroprotection, neuroplasticity and neurogenesis, are central to protection and recovery and represent the background of EDA. The biological reality of the nervous system is far more complex. In fact, there is an endogenous holistic process of neuroprotection and neurorecovery that should be approached therapeutically in an integrated way. The current tendency to exclusively frame drug activity in terms of single mechanisms and single focus effect might distract from other paradigms with greater explanatory power and hinder the development of more effective treatment strategies. A change of concept is required in pharmacological brain protection and recovery. Prospective considerations include an integrated pharmacological approach, focusing on drugs with multimodal activity and pleiotropic neuroprotective effect which are biological drugs, rather than single mechanism drugs, which usually are chemical drugs.

New Aspects of Graft-induced Central Plasticity and Neuroregeneration at T 10 in a Rat Model†

“…Additionally, we demonstrated the coexistence of graft-induced cholinergic (peripheral) and glutamatergic (central) neurotransmission in reinnervated skeletal IOAM (immunoblotting), which has not been discussed in his previous papers. Taken together, our new observations do not contradict GB's and Pizzi's conclusions, but they do support our hypothesis that PNG regeneration can be mediated by different types of spinal neurons (motor, sensory, interneuron), and therefore coexistence of the two neurotransmitter types is not surprising [87][88][89][90][91][92][93][94][95].…”

“…Regarding the small number of animals assessed, this effect was coincidental with the positive electrical stimulation. This observation could be interpreted in accordance with reports showing the influence of CERE on the biochemical mechanism of neuroprotection and neuro-recovery [1,8,18,[82][83][84][85][86][87][88][89][90]. We recommend a new study examining the neuroprotective effect of CERE medication in our grafting procedure model with more extensive CERE treatment up to four weeks and a longer follow up of 6 months, which might provide more detailed insight into its beneficial neuromodulation potency on central plasticity.…”

“…An advantage is its ability to penetrate the blood-spinal cord barrier. We hypothesized that the acute treatment with CERE resulted in a) cell protection in the region of surgical spinal cord injury by the grafting procedure, b) neuroregeneration, and c) neuro-recovery within both the cord and graft, according to promising reports and evidence from brain and spinal cord lesions [18,19,22,23,28,31,[86][87][88][89][90][91][92][93][94].…”

“…We made use of Cerebrolysin ® for pharmacological neuromodulation, a drug that has raised hope for the support of clinical neuroprotection, neuro-recovery and neuroregeneration following central nervous lesions [86][87][88][89][90][91][92]. Endogenous molecules (e.g., neurotrophic factors) are the most important players involved in CNS protection and recovery.…”

Gabapentin is neuroprotective through glutamate receptor-independent mechanisms in staurosporine-induced apoptosis of cultured rat cerebellar neurons

“…The concept of neuroprotection refers to strategies that may result in salvage or recovery of injured nervous tissue [4] and is mainly applicable to apoptotic neuronal death, which in contrast to necrosis takes enough time to allow for intervention.…”