Table 1 An Overview of G-CSF application in Hypoxia-schaemia Brain Injury Models

Acute ischaemic cerebral injury (MCAO)

Adult SD rats

100

s.c. injected immediately after injury for 7d

Reduced infarct volume & necrotic cells

[29]

Increased Egr-1 & VEGF expression levels

Stroke (BCAO)

adult male Swiss Webster mice

50

s.c. injected 30min afterocclusion for 4 to 7 consecutive days

Increased expression of G-CSF receptor

[36]

Decreased GRP78 expression & decreased ATF6 cleavage levels

Decreased apoptotic protein signalling (DRI1 & P53) & increased pro-survival signalling (OPAI)

Upregulated anti-apoptotic protein Bcle-2 and downregulated pro-apoptotic proteins Bax & Bak

Increased locomotor sensitisation

Cerebral ischaemia reperfusion (tMCAO)

Adult SD rats

50

s.c. injected 1h after restoring CBF for 5 consecutive days

Reduced infarct volume & oedema

[37]

Improved neurological function & reduced apoptotic neurons

Downregulated the activation of the JNK apoptosis pathway

Ischaemic brain injury (DHCA)

Newborn piglets

34

iv. 2h prior to inintiation of bypass

Reduced neuronal injury in the hippocampus

[38]

Focal cerebral ischaemia (MCAO)

Adult male SD rats

50

s.c. injected at the onset of reperfusion; 2nd injected at onset of reperfusion for 2d

Attenuated infarct volume & early neurological deficits

[39]

Elevated STAT3 phosphorylation & nuclear Pim-1 expression

Increased expression of cIAP2 & Bcl-2 & decreased caspase-3 & Bax levels

Hypoxia-ischaemia (RCCA ligation)

Neonatal SD rats

50

s.c. injected 1h after HI for 56

Less vacuolization, neuron loss & tissue breakqown

[33]

Increased brain weight & G-CSF receptor expression

Reduced cleaved caspase-3 activity

Increased expression of anti-apoptotic pathway mediators

Hypoxic-ischaemic brain damage (RCCA ligation)

Neonatal SD rats

50

s.c. injected 1h after HI for 6 days & 11 days

Promoted physical development & improved functional deficits

[40]

Reduced brain atrophy & increased systemic organ weight

Increased exploratory behaviour & shorm-term memory

Hypoxia- ischaemia (RCCA ligation)

Neonatal SD rat pups

50

s.c. injected 1h after HI

Reduced infarct volume & corticosterone levels

[41]

Decreased cleaved caspase-3 level & lowered Bax/Bcl-2 ratio

G-CSF did not influence ACTH response

Hypoxia- ischaemia (RCCA ligation)

Neonatal SD rat pups

50

s.c. or i.p. 1h after HI for 4d

Reduced infarct volume & lung injury

[30]

Increased neutrophil count & less brain tissue atrophy

Improved physical development & neurological function

Hypoxia-ischaemia (RCCA ligation)

Neonatal SD rat pups

50

s.c. injected 1h after HI

Reduced infarct volume & increased expression of G-CSF receptor in neurons

[42]

Increased p-AKt expression & decreased p-GSK-3β/GSK-3β ratio

Decreased aopototic markers & TUNEL positice cells in neuron

Perinatal hypoxia

Neonatal SD rat pups

10, 30, 50

s.c. injected 1d after HI

Attenuated PSD-95 protein expression levels & improved long-term deficits

[43]

Increased phosphorylated activity of pRaf-pERK1/2-PCREB pathway

Enhanced increase expression of neurogenesis in hippocampal neuron

Stroke (MCA ligation)

Adult male SD rats

15

s.c. injected 1h after restoring CBF for 15d

Decreased mortality rate & less effect in reducing infarct volume

[44]

Improved functional recovery of motor function

Increased number of proliferating cells & new neurons in the SVZ

Hypoxia-ischaemia (RCCA ligation)

Neonatal SD rats

50

i.p. immediately after HI induction

Attenuated cerebral infarction & improved body weight

[45]

Inhibited apoptosis by decreasing apoptotic cells & increased brain volume

Focal cerebral ischaemia (MCAO)

Male Wistar rats

60

iv 30min after occlusion

Reduced infarct volume & mortality rate

[46]

Increased STAT3 expression & anti-excitotoxic effect

Stroke (MCAO/CCA)

50

iv 60min after induction

Elevated neutrophil count & reduced infarct volume

[47]

Increased expression of G-CSF receptor in neurons

(MCAO)

60

iv 2h after onset of occlusion for 5d

Increased protein level of STAT3 & increased AKt phosphorylation

Improved long-term behaviour

Hypoxic-ischaemic brain injury (MCAO)

Neonatal mice pups

200

s.c. injected 1h after injury & 60h after injury for 5d

Did not improved neurobehavioural outcomes & brain injuries

[48]

Perinatal hypoxia

Neonatal rat pups

30

i.p. 1d after HI induction for 6d

Enhanced neurogenesis & improved long-term cognitive function

[49]

Hypoxia- ischaemia (RCCA ligation)

Neonatal SD rat pups

50

i.p. 2.5h after HI induction

Decreased expression levels of TNF-α and IL-1β & increased IL-10 levelsDecreased expression levels of TNF-α and IL-1β & increased IL-10 levels

[50]

Increased Bcl-2 expression levels & decreased CC3 and Bax expression levels

Upregulated p-mTOR and p-P70S6K protein expression levels

Hypoxia-ischaemia (RCCA ligation)

Neonatal SD rat pups

50

s.c. injected 1h after HI

Showed localisation of G-CSF receptor in enthothial cells

[51]

Decreased β-catenin and p120-catenin phosphorylationDecreased β-catenin and p120-catenin phosphorylation

Attenuated PICs (IKKβ, NF-κB, TNF-α, IL-1β) & enhanced IL-10 levelsAttenuated PICs (IKKβ, NF-κB, TNF-α, IL-1β) & enhanced IL-10 levels

Decreased adheren proteins & increased tight junction proteins expression

Hypoxia-ischaemia (RCCA ligation)

Neonatal SD rat pups

50

s.c. injected 1h after hypoxia

Inhibited corticosterone synthesis by activating its receptor in cortical cells

[52]

Increased expression of JAK2, PI3K, AKt and PDE3B proteins

Inhibited cAMP elevation induced by cholera toxin

Decreased infarct volume and increased body weight