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Table 2 Treatment with modern drugs of entering clinical trials in animal models post-TBI

From: Therapy of traumatic brain injury by modern agents and traditional Chinese medicine

Multipotential modern treatment strategies

Models

Species

Sample size

Gender

Mode of action

Effects on post-TBI consequences 

Corticosteroids [8,9,10,11]

CCI

Rat

36

Male

↓ the number of CD31+ cells and circulating EPCs

↓ neuronal cell loss and impaired neurofunction

 

CCI

Rat

296

Male

↑ MR; ↓GR

↓apoptosis and cell loss, and impaired spatial memory

 

CCI

Rat

Unknown

Male

↓ TGF-β1, IL-1β, TNF-α,↑ IL-10) ;↓ Bax, ↑Bcl-2

↓cavity size;↑neuronal cell survival and improved motor functional recovery

 

CCI

Rat

24

Male

↓NeuN+ and apoptotic cells; ↓ activated microglia/infiltrated macrophages ; ↓ IL-1β, TGF-β1, TNF-α, and IFN-γ

↓lesion volume; ↑motor and cognitive function

Citicoline [23,24,25]

WDI

Rat

30

Male

↓S-100β and NES

↑nerval protection effect

 

WDI

Rat

40

Male

↓S-100β and IL-6

↑brain functional recovery

 

WDI

Rat

40

Male

↓neurological severity score, balance test;↑slanting board test

↑ the recovery of neural dysfunction

β-blockers [20, 21]

CCI

Mouse

64

Male

↓leukocyte rolling; ↑GNT

↓edema

 

WDI

Mouse

100

Both sexes

↓p-tau

↓learning and memory deficit

Statins (atorvastatin, simvastatin, lovastatin) [28,29,30, 32]

WDI

Mouse

36

Male

↓TNF-α, IL-1β, TBK1,TLR4; ↓microglia activation

↓edema; ↓cognitive deficit

 

WDI

Rat

18

Male

↓TNF-α, IL-1β, NF-κB, CD40

↓TBI-induced intestinal injury

 

FPI

Rat

30

Male

↓ TLR4,NF-KB p65,p-IκB,cleaved Caspase-3, IL-6, TNF-α and IL-1β

↑neurological function

 

FPI

Rat

32

Male

↓GRP78, P-PERK,P-eif2α, ATF6,Caspase12,CHOP, Nrf2 and Caspase3

↓edema; ↑neurological function

Tranexamic acid [39,40,41,42]

WDI

Mouse

60

Male

↓ MCP-1 , IL-6, TNF-α, p-tau and NSE; ↑ MIP-1α

↓ neuroinflammatory response

 

CCI

Pig

20

Female

↓ p-tau and IL-1β

↑neurological function

 

CCI

Mouse

Unknown

Male

↑immune activation at the 72 h, altere several myeloid and lymphoid cell populations

↑immune-modulatory properties

 

CCI

Mouse

Unknown

Both sexes

↓ blood neutrophils in male mice 3 h post-TBI, ↑ monocyte subsets and dendritic cells

protective effects post-TBI but only in male mice

Erythropoietin [46,47,48,49]

WDI

Rat

15

Male

↑BDNF and SDF-1; ↓NSE

↑anti-inflammatory properties

 

CCI

Rat

76

Unknown

↓NF-κB and GR; ↑GPX, SOD, GSH/GSSG and HIF-1α

↓apoptosis and cell loss

 

WDI

Mouse

Unknown

Male

↓GFAP and S100; ↑MAPK, cAMP, CREB and NOR

↑memory response, hippocampal neuroprotection, and neurogenesis

 

WDI

Rat

20

Male

↑AQP4, ↓GFAP

↓brain edema

Progesterone [13,14,15,16,17]

CCI

Rat

121

Both sexes

↑NOR, EAAT-3 and NaVβ3; ↓EPSCs,IPSCs, frequency and EPSC amplitude

↑motor and memory functional recovery

 

CCI

Rat

36

Female

↓ICP;↑CPP

↓ cerebral edema; ↓learning and memory deficit

 

WDI

Rat

48

Male

↓Bcl-2; ↑BAX

↑motor and cognitive function

 

WDI

Rat

210

Female

↑SOCS-3, p-STAT-3, NFκB-P52, p-NFκB-P65 and p-IκBα

↓ brain edema

 

WDI

Rat

Unknown

Female

↑NGF; ↓ IL6

↓ cerebral edema

Amantadine [54, 55]

CCI

Rat

60

Male

↓ the numbers of degenerating neurons

↓brain lesion; ↓learning and memory deficit

 

WDI

Rat

Unknown

Male

↓ DNA fragmentation

↓ neuronal cell loss and impaired neurofunction

Caffeine [62,63,64]

FPI

Rat

180

Male

↓lethal apnea (an acute bolus of caffeine)

↑motor function

 

WDI

Rat

56

Male

↑spine density in OFC, mPFC and NAc; ↓telomere length

↓motor and cognitive function

 

WDI

Rat

64

Both sexes

↑Drd1, Drd2, Gfap, Dnmt3a and longer telomeres

↓anxiolytic-like behaviors

  1. CCI controlled cortical impact, WDI weight drop injury, FPI fluid percussion injury, EPCs endothelial progenitor cells, MR mineralocorticoid receptor, GR glucocorticoid receptor, GNT garcia neurologic test, p-tau phosphorylated tau, NF-κB nuclear transcription factor-κB, IκB inhibitor of NF-κB, NSE neuron-specific enolase, GRP78 glucose-regulated protein 78, PERK proteinkinaseR—likeERkinase, eIF2α eukaryotic tanslation initiation factor 2α, ATF6 activating transcription factor, Caspase 3 cysteme aspartate specific protease 3, Caspase 12 cysteme aspartate specific protease 12, CHOP CAAT/enhancer binding protein homologous protein, Nrf2 nuclear factor (erythroidderived 2)-like 2, MCP-1 monocyte Chemoattractant Protein-1, MIP-1α macrophage inflammatory protein 1α, SDF-1 stromal cell-derived factor 1, GPx glutathione peroxidase, GSH reduced glutathione, GSSG oxidized glutathione, GR glutathione reductase, SOD superoxide dismutase, NOR novel object recognition, MAPK mitogen-activated protein kinase, cAMP cyclic adenosine monophosphate, AQP4 aquaporin 4, GFAP glial fibrillary acidic protein, EPSCs excitatory post-synaptic currents, IPSCs inhibitory post-synaptic currents, EAAT3 excitatory amino acid transporter 3, NaVβ3 β subunit of the voltage-gated sodium channel, ICP Intracranial pressure, CPP cerebral perfusion pressure, SOCS-3 suppressor of cytokine signaling-3, STAT-3 signal transducer and activator of transcription-3