Neurobiological Links between Stress, Brain Injury, and Disease

Table 3

Neurobiological links between stress and brain injuries/diseases.

Compound stress model	Cognitive dysfunction and mechanism	Potential therapeutic target	Reference
Stress+AD	Stress aggravates cognitive impairments and neurodegeneration; (1) Inhibition of AQP4; (2) Aβ and p-Tau accumulation↑; (3) Aβ clearance rate↓; (4) Increased Aβ production; (5) ROS↑; (6) Metabolic disorders	Glucocorticoid inhibitor; HPA axis inhibitor; Autophagy activator; AQP4 activator; Antioxidant drugs	[5, 105, 109, 110, 112, 114, 115, 117]
Stress+Stroke	Brain lesions, cognitive deficits, and neurodegeneration↑; (1) Prevents angiogenesis; (2) Overactivation of ERS and inhibition of astrocytes, microglia; (3) ROS, neuroinflammation, and glutamate↑; (4) Glucose utilization, TJ-related protein degradation↑	Vasoactive drugs; Anti-inflammatory drug; Antioxidant drugs	[122, 123, 125–128, 131, 132, 141]
Stress+TBI	Cognitive impairment, lesion volume↑; (1) MCP-1, MIP-1α, TNF-α, and IL-6↑; (2) BDNF generation↓; (3) Activates ER stress-mediated neurodegeneration; (4) Disorders of HPA axis	Anti-inflammatory drug; BDNF; ERS inhibitor, such as salubrinal; Antioxidant drugs	[9, 142, 144–146, 165, 172, 173]
Stress+Epilepsy	Increases susceptibility to epilepsy; Hippocampal ERS; Oxidative stress↑	ERS inhibitor, such as TUDCA	[67, 79, 165–167, 174]

Note: AD: Alzheimer’s disease; TBI: traumatic brain injury; ERS: endoplasmic reticulum stress; TJ: tight junction; BDNF: brain-derived neurotrophic factor; ROS: reactive oxygen species; HPA: hypothalamus-pituitary-adrenal; ↑: upregulated; ↓: downregulated.