Neurosurgery notes/Trauma/Secondary head injury/Cerebral metabolism

Cerebral metabolism

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Secondary head injury
Perturbations in cerebral metabolism
  • TBI damages mitochondrial functionality to propagate neurodegeneration and limit neuroregeneration.
  • Severe TBI → induces a sudden shift from aerobic metabolism to hyperglycolysis/anaerobic metabolism + high glucose turnover → cerebral acidosis → Acidosis shifts the haemoglobin oxygen- dissociation curve to the right → increase O2 supply influx to injured brain tissue
  • Hyperglycolysis
    • Occurs even when sufficient oxygen is present
    • Occurs in 56% of patients (on PET) within 1 week following TBI.
  • CSF lactate
    • Elevated CSF lactate after TBI
      • Typically normalizes within 12 hours of injury
      • Except following cerebral ischaemia and diffuse cerebral swelling.
    • Role of lactate in injured brain energetics is controversial,
      • Metabolic waste
      • Supplemental fuel
      • Neuroprotection
      • Signalling molecule in cortical neurons
    • Measurement of CSF lactate
    • Methods of reducing CSF lactate
      • Via Pentose phosphate pathway (PPP)
          • Increased activity of the PPP after severe TBI allows brain to increase cerebral glucose uptake without an increase in
            • CMRO2
            • Lactate production
          • PPP
            • Does not use oxygen as substrate
            • Does not produce ATP
            • Serves as an antioxidant that contributes to the shift in glucose metabolism from glycolysis to PPP in ischaemic brain tissue.
          • Infusion of isotype glucose after TBI increased
            • PPP activity by 19.6% compared to 6.9% in controls.
          • The PPP products (NADPH, ribose 5- phosphate, and erythrose 4- phosphate) can
            • Upregulate fatty acid synthesis,
            • Upregulate DNA repair and replication, and
            • Increase amino acid and neurotransmitter production
            • Combat oxidative stress
              • NADPH is used to produce
                • Reduced forms of glutathione and thioredoxin,
                • Cofactors for glutathione peroxidases, and peroxiredoxins
          Pentose phosphate pathway. The pentose phosphate pathway (PPP) is an alternative pathway for glucose utilization and is found to be upregulated following TBI. It provides several biochemical substrates that are potentially protective, and this is an actively explored research avenue.
          Pentose phosphate pathway. The pentose phosphate pathway (PPP) is an alternative pathway for glucose utilization and is found to be upregulated following TBI. It provides several biochemical substrates that are potentially protective, and this is an actively explored research avenue.
          notion image
    • CMRO2 (Cerebral metabolic rate of oxygen)
      • The rate of oxygen consumption by the brain
      • In TBI patients,
        • 30% patients are found to have CMRO2 values drop even in non-ischaemic conditions from normal value of 3.3 ml/ 100 g/ min to 1.2– 2.3 ml/ 100 g/ min.
      • While CMRO2 after TBI correlate with
        • GCS and
        • A strong predictor for neurologic outcome,
        • Reduced CMRO2 does not necessarily result from ischaemia nor directly cause patient decline.
      • Studies of severe TBI with mean GCS of 6 report a (despite absence of ischaemia)
        • 25% incidence of reduced oxidative metabolism
        • Persistent metabolic crisis (elevated LPR (cerebral lactate/ pyruvate ratio) >40)
    • LPR (lactate pyruvate ratio)
    • Published studies using 15-O-PET demonstrate a metabolism threshold of 37.6 μmol/ 100 ml/ min resulting in irreversible injury.