Citation

Mastrorilli V, Farioli Vecchioli S. Neural Regen. Res. 2024; 19(3): 475-476.

Copyright

(Copyright © 2024, Neural Regeneration Research, Shenyang, Liaoning Province, P.R. China, Publisher Wolters Kluwer)

DOI

10.4103/1673-5374.380888

PMID

37721260

Abstract

Is it better to be safe than sorry? This Hamletic dilemma has always stimulated medical-scientific debates in numerous fields of biomedicine. And among these, the preventive-therapeutic approach to the treatment of brain trauma is one of the most striking examples. Traumatic brain injury (TBI) is a leading cause of brain damage among young and elderly populations with a very high hospitalization and death rate. TBI is characterized by two pathologically distinct but strictly consequential phases: a first characterized by an immediate and highly variable mechanical dysfunction of the brain tissue, which involves widespread cell death and tissue degeneration, followed by a second phase which can last from days to even years depending on the severity of the TBI and the patient's pre-existing health status. Secondary processes, including inflammatory phenomena, oxidative stress associated with metabolic, vascular, and neuro-modulatory deficits, are very often responsible for neuro-motor and psychological deficits leading to long-term disabilities (Kaur and Sharma, 2018). In recent years, physical activity has emerged as one of the most promising non-pharmacological therapies in post-traumatic neuro-rehabilitation strategies (Coll-Andreu et al., 2022). However, pre-clinical experimental evidence and human clinical trials have not yet produced unequivocal results capable of establishing standardized therapeutic pathways based on post-traumatic exercise. The high diversity of short- and long-term consequences of head trauma, which can range from motor and cognitive problems to sleep-related problems and mood, up to the comorbidity of the onset of neurodegenerative diseases such as Alzheimer's diasease, represents one of the main obstacles to determine how much and when physical therapy can bring benefits in a post-traumatic patient (Griesbach et al., 2018). Furthermore, in this context, the age and previous psycho-physical conditions of the traumatized patient must also be taken into account. These issues represent fundamental variables that can greatly modify the optimal conditions of physical activity capable of providing an effective therapeutic benefit. With reference to when to subject the patient to physical therapy, some preclinical studies have shown that a therapeutic approach based on very early physical activity post-trauma can lead to an aggravation of the progression of post-traumatic neuro-degenerative processes, due to various deleterious factors such as an increase in inflammatory phenomena, the hypersecretion of catabolic hormones, an altered ion homeostasis and Na+-K ATPase activity and finally the increase in metabolic demand within an already compromised brain (Griesbach, 2011). Further clues concerning a deleterious effect of a premature approach to post-TBI physical activity come from studies in which a lack of increase in brain-derived neurotrophic factor (BDNF), cAMP-response element binding protein, synapsin, and other signaling molecules involved in synaptic plasticity was observed in mice subjected to physical activity in a period very close to TBI, with consequent impairments in post-lesion cognitive abilities. Finally, the negative effect of early post-traumatic physical activity is also reflected in the abrogation of different endogenous compensatory mechanisms, suggesting that an engaging prematurely in post-TBI physical activity can induce a significant lowering of the endogenous mechanisms responsible for restoring cerebral homeostasis and the stimulation of reparative neuroplasticity (Coll-Andreu et al., 2022).

Language: en