1. PRESENTER: DR SONIA
NEUROANAESTHESIA
PGIMER

2. an impact, penetration or rapid movement
of the brain within the skull that results in
altered mental state.
DEFINITION

3. CLASSIFICATION
•PRIMARY
INJURY
•SECONDARY
INJURY
•MILD
(13-15)
•MODERATE
(9-12)
•SEVERE
(<9)

4. Primary injury: consequence of direct
impact.( coup/ countercoup)
Secondary injury: due to subesquent
events.

5. Why??????
Common than any other neurological
disease or event
Poor prognosis
High morbidity and mortality

6. TBI
NEUROCHEM
-ICAL
FACTORS
BBB AND
CBF
DISRUPTI-
ON
GLUCOSE
METABOLISM
INFLAMM
-ATION
AND FREE
RADICALS

9. CEREBRAL BLOOD FLOW
Significant alteration in CBF
In experimental animal models -mild to
moderate TBI, showed a significant drop off
in blood flow (70-80% of normal) , and with
more severe injury the drop off neared
ischemic levels.

10. Some association with stroke.
Morphological injury
hypotension in the presence of
autoregulatory failure
inadequate availability of nitric oxide or
cholinergic neurotransmitters,
potentiation of prostaglandin-induced
vasoconstriction.

11. Cerebral hyperemia –can present in the
initial stage leading to cerebral edema and
raised ICP.

12. Cerebrovascular autoregulation and CO2-
reactivity
Hyperemia in a setting of impaired
autoregulation is generally associated
with intractable increases in intracranial
pressure and ultimately, poorer cerebral
perfusion and worse
outcome.(breakthrough phenomenon)
CO2 reactivity –may be preserved.

14. CEREBRAL VASOSPASM
Seen in one third patients
Post traumatic day 2-5
Endothelial dysfunction, decreased NO.

15. BBB DYSFUNCTION
Due to mechanical damage
Becomes permeable to blood borne
factors
Activation of coagulation cascade-
thrombus- ischemic injury
Pro-inflammatory mediators, activation
of cell adhesion molecules
Vasogenic and cytotoxic edema

17. IONIC FLUX AND GLUTAMATE
Redistribution of ions and
neurotransmitters, altering the membrane
potential
GLUTAMATE
K+,Ca2+

18. 18
Potassium
release into
ECS
Excitoxicity, precipitated by the
neurotransmitter glutamate
Failure of
presynaptic
membrane ion
pumps
Initial
depolarisation
dependant
release of
GLUTAMATE
Conventional
Theory
RecentOpinion
Release of
CALCIUM
Trauma-induces
changes to
postsynaptic
Glutamate
receptor -
pharmacology,
kinetics and
composition
AMPA receptor
NMDA Receptor
AMPA - -amino-3-hydroxy-5-methyl-4-isoxazleproprionic acid
NMDA - N-methyl-D-aspartic acid
• Increased current response to
AMPA-receptor agonists
• Reduction in expression of
receptors containing the GluR2
subunit (I.e. more permeable to Ca)
• Thought to be mediated by TNF- 
Release of
CALCIU
M
• Generation of neuronal nitric oxide
(a free radical)
• Increased production of of free
radicals (due to high mitochondrial
Ca) mixes with NO to form
Peroxynitrite
• Nitration
• Lipid peroxidation
• DNA fragmentation
CELLULAR DAMAGE

19. 19
Protease NO
synthas
e
Phospolipas
e A2
Endonuclease
s
Protein
kinases
phosphatas
es
Cytoskeleto
n
breakdown
Mitochondr
ial damage
Lipid
peroxidation
membrane
damage
DNA
fragmentatio
n
“Secondary”
genes
Apoptosis
Free
radicals
Notric
oxide
Arachidon
ic acid
CA2+ INFLUX LEADING TO
DESTRUCTIVE CASCADE

21. Cerebral glucose metabolism in
TBI
Initial phase of hyperglycolysis followed
by decraesed glucose metabolism
This initial increase in CMRglc is due to
an increased requirement of cellular
energy to restore the ionic balance and
neuronal membrane potential.

22. Hyperglycolysis has been observed
within the first 8 days after severe human
head injury.
Increase in glucose metabolism may or
may not be accompanied by increase in
the CBF, leading to uncoupling of the
CMRO2/CBF ratio

23. Activation of anaerobic pathways
followed by accumulation of lactate.
Increase in the lactate levels in CSF,
altered lactate/ pyruvate ratio and
negative A-V difference in the lactate
levels.

24. Decreased glucose uptake-
decreased CBF(uncoupling)
defects in glucose transporter function
decreased metabolic demand for glucose.

25. Adult rat studies have shown decreased
neuronal glucose transporter (GLUT1)
immunoreactivity 2-4 hours after FP
injury
18F-DG kinetic changes following
moderate to severe TBI in humans have
determined that hexokinase activity was
globally decreased, with glucose transport
impairments occurring specifically within
the contusion sites.

26. Inhibition of the glycolytic pathway:
Increased activity of pentose phosphate
pathway
Decreased NAD+ levels
Decreased activity of PDH
POST TBI ENERGY CRISIS

28. Reactive molecules with unpaired electrons.
ROS and RNS.
˙OH , ONOOˉ, O2˙ˉ, H2O2, NO˙
Scavengers- superoxide dismutase(SOD),
glutathione peroxidase, vit E, C, catalase.
FREE RADICALS IN TBI

30. Lipid peroxidation of polyunsaturated fatty acids
Oxidation or nitration of proteins
Activation of DNA repair enzymes (PARP)

31. ROLE OF MITOCHONDRIA
Two mechanisms
Ca2+ influx
Free radical damage
Apootosis vs necrosis

33. NEUROINFLAMMATION
More with contusions and hemorrhages
Surge for pro-inflammatory mediators
Followed by increased synthesis of
chemokines and cell adhesion molecules
(ICAM -1, V-CAM 1) leading to influx of
inflammatory cells, though the direct
invasion of WBC,s is not there.

34. Target – by monoclonal antibodies.
Upregulation of IL-1, TNF-ß within hours
after the injury
Affects the normal tissue, leading to scar
formation.

37. THANK YOU