Table 3.
Divergent Biochemical Responses among Injury Groups Across Key Cellular Processes
| Cell process | 30-min MCAO | 2-h MCAO | TBI (CCI) |
|---|---|---|---|
| Energy metabolism Comparison: 30-min > 2-h MCAO 2-h MCAO ≠ TBI |
↑Transketolase (pentose phosphate to GAPDH) – Phosphoglycerate kinase (+ATP) ↑ Neuron-specific enolase ↑ Pyruvate kinase (+ATP) (ATP production) |
↑Transketolase (pentose phosphate to GAPDH) ↓Phosphoglycerate kinase (+ATP) ↑ Neuron-specific enolase ↓ Pyruvate kinase (+ATP) (degraded ATP production) |
N/A ↓Phosphoglycerate kinase (+ATP) ↓ Neuron-specific enolase ↓ Pyruvate kinase (+ATP) (degraded ATP production) |
| ↓Pyruvate dehydrogenase ↓ Malate dehydrogenase (lost aerobic respiration) |
↓Pyruvate dehydrogenase ↓ Malate dehydrogenase (lost aerobic respiration) |
↑Malate dehydrogenase (malate shuttle active; aerobic respiration possible) |
|
| Synaptic function Comparison: 30-min ≠ 2-h MCAO 2-h MCAO = TBI |
↓Vesicle ATPase (less ATP and less neurotransmitter) |
↓Neurotransmitter update ↓ Vesicle trafficking ↓ Vesicle docking/exocytosis ↓ Vesicle endocytosis ↓ Vesicle recycling (lost synaptic vesicle cycle) |
↓Neurotransmitter update ↓ Vesicle trafficking ↓ Vesicle docking/exocytosis ↓ Vesicle endocytosis ↓ Vesicle recycling (lost synaptic vesicle cycle) |
| ↓Transgelin 3 (signaling dysfunction) |
↓Map-tau, and spectrins ↓ Tubulins, actin, map 1 and 2 ↓ Transgelin 3 (degraded cytoarchitecture) |
↓Map-tau, and spectrins ↓ Tubulins, actin, map 1 and 2 ↓ Transgelin 3 (degraded cytoarchitecture) |
|
| ↑Neurogranin (synaptic plasticity) |
N/A | N/A | |
| Chaperone activity Comparison: 30-min > 2-h MCAO 2-h MCAO > TBI |
↑HSP70, ↓p-STIP1, ↑HSP90 (upregulated HSP70 and HSP90 activity) |
↑HSP70, – p-STIP1, – HSP90 (less HSP70 and HSP90 activity) |
↓HSP70 (lost HSP70 activity) |
| N/A | ↓SGTA, ↑HSP10 (efficient use of HSP60 complex) |
N/A | |
| Cell survival factors Comparison: 30-min < 2-h MCAO 2-h MCAO ≠ TBI |
↑PRDX (antioxidant) (to reduce TNF-induced apoptosis) |
↑PRDX (antioxidant) ↑ Fetuin-B (calpain/caspase inhibitor) (to reduce apoptosis) |
↑Fetuin-B (protease inhibitor) (to reduce apoptosis-associated calpain and caspase activity) |
| ↓Calcineurin (to reduce apoptosis) |
↓Calcineurin ↓ Free 14-3-3's (to reduce apoptosis) |
↑Free 14-3-3's (uninhibited apoptosis) |
GAPDH, glyceraldehyde-3-phosphate dehydrogenase; ATP, adenosine triphosphate; MCAO, middle cerebral artery occlusion; TBI, traumatic brain injury; HSP70, heat shock protein 70; p-STIP1, phosphorylated stress-induced phosphoprotein 1; HSP90, heat shock protein 90; SGTA, small glutamine-rich tetratricopeptide-repeat containing protein A; HSP10, heat shock protein 10; PRDX, peroxiredoxin 2.