1. Dr Sunil Munakomi COMSTH, Nepal
Newer insights to TBI
Dr Sunil Munakomi
COMSTH, Nepal

2. TBI A silent epidemic. A major public health burden.
Langlois JA, Sattin RW. Traumatic brain injury in the united states: Research and programs of the centers for disease control and prevention (CDC) J Head Trauma Rehabil. 2005;20:187–188.
A major public health burden.
Corrigan JD, Selassie AW, Orman JA. The epidemiology of traumatic brain injury. J Head Trauma Rehabil Mar-Apr;25(2):72-80.

3. Impact Major cause of death, especially among young adults.
Leads to multispectral disabilities among the survivors.
Maas AIR, Stocchetti N, Bullock R. Moderate and severe traumatic brain injury in adults. Lancet Neurol. 2008; 7: 728–741.

4. Aim of the presentation
Enlighten upon newer insights to the pathogenesis of TBI.

5. Glutamate toxicity
Astrocytic glutamate transporters like GLAST and GLT-1 and splice variant are down regulated shortly following the insult.
Yi J. H. & Hazell A. S. Excitotoxic mechanisms and the role of astrocytic glutamate transporters in traumatic brain injury. Neurochem. Int. 48, 394–403 (2006).
Initiate and accelerate the process of apoptosis and parthanatos.

7. Critique
Extracellular glutamate level in TBI is cleared within 5 minutes.
Spreading depression due to the sodium extrusion, sequelae of calcium influx, and subsequent hyperpolarisation to be the cause of the phenomenon.
Obrenovitch T. P., Urenjak J. (1997). Is high extracellular glutamate the key to excitotoxicity in traumatic brain injury? J. Neurotrauma 14, 677– /neu

8. Lactate storm Lactate peak within minutes following severe TBI.
Kraig RP, Petito CK, Plum F, Pulsinelli WA. Hydrogen ions kill brain at concentrations reached in ischemia. J Cereb Blood Flow Metab 1987 Aug;7(4):
There is a glial–neuronal uncoupling resulting in a lactate storm.
Extracellular lactate increase is independent of brain hypoxic ischemia in severe TBI.
Sala N, Suys T, Zerlauth JB, Bouzat P, Messerer M, Bloch J, et al. Cerebral extracellular lactate increase is predominantly nonischemic in patients with severe traumatic brain injury. J Cereb Blood Flow Metab 2013 Aug 21.

9. Number of studies have verified the implication of raised lactate level in the CSF and the MR spectroscopy and the subsequent outcome in the patients with TBI.
Toczylowska B, Chalimoniuk M, Wodowska M, Mayzner-Zawadzk E. Changes in concentration of cerebrospinal fluid components in patients with traumatic brain injury. Brain Res (2006) 1104:183– /j.brainres
Kamada K, Houkin K, Hida K, Iwasaki Y, Abe H. Serial changes in metabolism and histology in the cold-injury trauma rat brain model. Proton magnetic resonance imaging and spectroscopy study.Neurol Med Chir (Tokyo) 1995;35:1–7.

11. Lactate - a friend or foe ???
Lactate as a supplementary fuel to the brain can a friend only in an aerobic environment.
Lactate substitution is in fact a foe in such a lethal and stormy metabolic milieu.
Bouzat P, Oddo M. Lactate and the injured brain: friend or foe? Curr Opin Crit Care. 2014;20:133–140.

12. G Lymphatics and Taupathy
Facilitates the clearance of interstitial solutes, including amyloid, from the brain.
Chronic impairment of this pathway renders the post-traumatic brain vulnerable to tau aggregation and the onset of neuro-degeneration thereafter.
Johnson VE, Stewart W, Smith DH. Traumatic brain injury and amyloid-β pathology: a link to Alzheimer’s disease? Nature reviews Neuroscience. 2010;11(5):
Scott G, Ramlackhansingh AF, Edison P, et al. Amyloid pathology and axonal injury after brain trauma. Neurology. 2016;86(9):

13. Chronic traumatic encephalopathy
TBI can prime microglia.
With repeated trauma, the switching process of these cells from neurotrophic to ramified reparative mode does not occur.
Blaylock RL, Maroon J. Immunoexcitotoxicity as a central mechanism in chronic traumatic encephalopathy—A unifying hypothesis. Surgical Neurology International. 2011;2:107. doi: /

15. Sleep architecture in head injury
Sleep promotes enhanced cerebrospinal fluid (CSF) to interstitial fluid (ISF) exchange.
Prudent for timely restoration of the internal milieu inside the brain for its efficient functioning.
Xie et al “Sleep initiated fluid flux drives metabolite clearance from the adult brain.” Science, October 18, 2013.
Lateral and supine positions are more favorable for this clearance process.
Lee H, Xie L, Yu M, et al. The Effect of Body Posture on Brain Glymphatic Transport. The Journal of Neuroscience. 2015;35(31):

16. N3 phase of slow wave sleep (SWS) decreases CMR02 thereby minimizing metabolic demand.
Matthews EE. Sleep Disturbances and Fatigue in Critically Ill Patients. AACN advanced critical care. 2011;22(3):
Growth hormone pulsatile release accelerates tissue healing and hastens recovery .
Kamdar BB, Needham DM, Collop NA. Sleep Deprivation in Critical Illness: Its Role in Physical and Psychological Recovery. Journal of Intensive Care Medicine. 2012;27(2):

19. Take home message
These newer avenues can be a silver lining in our quest to manage traumatic brain storm.
Multimodal approach to be implemented.
Can help our transition from nihilism to optimism in managing TBI.

20. Not just flogging a dead horse

21. THANK YOU