Table 1 Summary of the main topics discussed in this review

Underlying mechanisms of sepsis

a. Sepsis modeling in animals

[8,9,10,11,12]

b. From systemic inflammation to neuroinflammation and BBB dysfunction

- Systemic inflammation

[3, 13,14,15,16,17,18]

- Neuroinflammation

[19,20,21,22,23,24,25, 27,28,29,30,31,32,33]

- BBB dysfunction

[34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50]

c. Ischemia/hypoperfusion

[5, 51,52,53,54,55,56,57]

d. Aβ and tau protein accumulation

[58,59,60,61,62,63,64,65,66,67,68,69]

- GSK3β

[70,71,72,73,74,75,76,77]

- RAGE

[60, 63, 78,79,80,81,82,83,84,85,86,87,88]

e. Direct brain damage

[89, 90]

Neurological manifestations of sepsis-associated brain injury

a. The spectrum of acute cognitive impairments in sepsis

[91, 93, 94]

- Sepsis-associated encephalopathy

[29, 91, 94,95,96]

- Delirium

[97,98,99,100]

- Sickness behavior

[101,102,103,104]

b. Long-term cognitive impairments in sepsis

[4,5,6, 91, 94, 105,106,107]

Imaging findings in sepsis-associated brain injury

[39, 89, 92, 108,109,110, 112,113,114,115,116,117]

Potential therapeutic strategies

a. Acute phase therapeutic strategies

- Antibiotics

[5, 118,119,120,121]

- Targeting proinflammatory cytokines

[4, 103, 122,123,124,125]

- Prevention of hypovolemia and cerebral ischemia

[39, 126,127,128,129,130,131,132]

b. Long-term therapeutic strategies

- Targeting neuroinflammation

[26,27,28, 133,134,135,136,137,138,139]

- Target BBB

[39, 40, 42,43,44, 140,141,142,143,144,145,146]

- Targeting Aβ and tau phosphorylation

[58, 59, 61,62,63, 147]

- Targeting GSK3β

[70, 71, 148, 149]

- Targeting RAGE

[60, 63, 78, 79, 85, 150,151,152]