Recovery from brain trauma like injury or a stroke is a complex process and one that is not yet under precise human control. More often than not, the process of resumption of blood flow to injured parts of the brain also creates additional damage. In addition to physical damage, exposure to extreme conditions like sub-zero temperatures as well as extremely hot conditions can also result in damage to neurons.

Pharmacological options to help recovery from stroke as well as physical brain injury are limited. Patients are often left paralyzed after a stroke. One approach, to get around the fact that only a small number of post hoc curative options are available in this area of medicine, has been to pre-condition the physiological system to withstand trauma. Several plant-derived substances as well as synthetic ones have been tried out to help the brain adjust to adverse environmental conditions (very cold and very hot) as well as to physiological insults like deprivation of oxygen. These “adaptogens” or molecules that help to adapt have been known as nootropic molecules or simply nootropics. Some nootropics like an extract from Bacopa monnieri also help to enhance memory and cognitive functions even in the absence of brain trauma.

The list of known nootropics is growing and the latest molecules to join the club are Cerebrolysin and GYKI-52466. Cerebrolysin is a mixture of neuropeptides that promotes growth of neurons, thereby diminishing the impact of environmental insults. GYKI-52466 is an anti-convulsant drug.

Exposure to very hot conditions has been shown to induce neurological and behavioral changes in experimental animal models. Rats exposed to whole body hyperthermia (4 hours at ambient temperature of 38C displayed behavioral changes and impaired motor functions. Neurotransmitters like glutamate and aspartate were elevated in these rats whereas the levels of glycine and GABA had reduced under these conditions. Anatomical studies also revealed damage to neurons as well as glial cells and a breakdown of the blood-brain barrier. Usually, the blood-brain barrier in cranial blood vessels is stringently permeable to very few substances. A breakdown in the blood-brain barrier signifies greater chances of permeation of blood borne toxins and viruses into neural tissue.

These effects of exposure of the whole body to extremely hot conditions can be reversed by administration of Cerebrolysin, if it is given within one hour of exposure. In experiments carried out by Drs. Sharma, Sharma, Mossler and Muresanu, damage to brain cells could be prevented if the animals were given Cerebrolysin 30 minutes prior to exposure to high heat or within one hour post exposure. Delayed administration of Cerebrolysin did not help recovery from brain damage resulting from these conditions.

These findings are important in light of the fact that exposure of people to such temperatures is possible. Consider the daytime temperatures in places like hot deserts where temperatures of 49 degrees Celsius (Thar Desert, India), 40C (Great Victoria Desert, Australia), 58C (Sahara Desert, Libya), 50C (Gobi Desert, Mongolia) have been recorded in summer. The Afar depression in Ethiopia, which incidentally is inhabited by humans, has daytime temperatures of 48C in summer with the highest recorded temperature being 64.4C. In steel mills, in some of the hottest sections, workers may be exposed to ambient temperature of 56C.

Nootropics like Cerebrolysin may help to recover from the damage caused by whole body hyperthermia in these situations, particularly in the manufacturing industry. People from endemic cultures of hot desert regions have presumably adapted to living under these conditions and the effects of administration of nootropics to such people is probably a whole new area of investigation. However, if occasional exposure is indicated for people who otherwise would remain in a comfortable ambiance, then treatment with cerebrolysin would perhaps help to reduce the damage caused by whole body hyperthermia.

GYKI-52466 is an antagonist of the glutamate receptor which is primarily used to treat convulsions and acts as a skeletal muscle relaxant. In a recent paper, Drs. Nayak and Kerr have described experiments conducted on rats where administration of low doses of GYKI-52466 helped to reduce the extent of brain damage resulting from an induced stroke. Loss of brain tissue was lesser in animals pre-treated with GYKI-52466 than that seen in control animals which were not given the drug. Behavioral traits were also less affected in rats treated with GYKI-52466 as compared to animals not exposed to the drug.

Research into both these nootropics is in progress and accumulation of more data is certainly warranted. However, there seems to be evidence that favors prophylactic prescription of such drugs to people who are at greater risk of suffering from hyperthermia or stroke.

References

Masliah E, & Díez-Tejedor E (2012). The pharmacology of neurotrophic treatment with Cerebrolysin: brain protection and repair to counteract pathologies of acute and chronic neurological disorders. Drugs of today (Barcelona, Spain : 1998), 48 Suppl A, 3-24 PMID: 22514792

Nayak PK, & Kerr DS (2012). Low-dose GYKI-52466: Prophylactic preconditioning confers long-term neuroprotection and functional recovery following hypoxic-ischaemic brain injury. Neuroscience PMID: 23246617

Sharma HS, Sharma A, Mössler H, & Muresanu DF (2012). Neuroprotective effects of cerebrolysin, a combination of different active fragments of neurotrophic factors and peptides on the whole body hyperthermia-induced neurotoxicity: modulatory roles of co-morbidity factors and nanoparticle intoxication. International review of neurobiology, 102, 249-76 PMID: 22748833

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