Abstract
Objectives: Neonatal hypoxia ischemia (HI) is an injury that can lead to neurological impairments such as behavioral and learning disabilities. Granulocyte-colony stimulating factor (G-CSF) has been demonstrated to be neuroprotective in ischemic stroke however it has also been shown to induce neutrophilia, ultimately exacerbating neuronal injury. Our hypothesis is that coadministration of anti-neutrophil antibody (Ab) with G-CSF will decrease blood neutrophil counts thereby reducing infarct volume and improving neurological function post HI brain injury. Methods: Rat pups were subjected to unilateral carotid artery ligation followed by 2.5. h of hypoxia. Animals were randomly assigned to five groups: Sham (n = 15), vehicle (HI, n = 15), HI with G-CSF treatment (n = 15), HI with G-CSF + Ab treatment (n = 15), and HI with Ab treatment (n = 15). Ab (325 μg/kg) was administered intraperitoneally while G-CSF (50 μg/kg) was administered subcutaneously 1. h post HI followed by daily injections for 3 consecutive days. Animals were euthanized at 96. h post HI for blood neutrophil counts and brain infarct volume measurements as well as at 5. weeks for neurological function testing and brain weight measurements. Lung and spleen weights at both time points were further analyzed. Results: The G-CSF treatment group showed tendencies to reduce infarct volume and improve neurological function while significantly increasing neutrophil counts. On the other hand, the G-CSF + Ab group significantly reduced infarct volume, improved neurological function and decreased neutrophil counts. The Ab alone group showed reversal of the neuroprotective effects of the G-CSF + Ab group. No significant differences were found in peripheral organ weights between groups. Conclusion: Our data suggest that coadministration of G-CSF with Ab not only prevented brain atrophy but also significantly improved neurological function by decreasing blood neutrophil counts. Hence the neuroprotective effects of G-CSF may be further enhanced if neutrophilia is avoided.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 192-199 |
| Number of pages | 8 |
| Journal | Neurobiology of Disease |
| Volume | 69 |
| DOIs | |
| State | Published - 2014 |
| Externally published | Yes |
Fingerprint
Keywords
- Anti-neutrophil antibody (Ab)
- Granulocyte-colony stimulating factor (G-CSF)
- Hypoxia-ischemia (HI)
- Neonatal
- Neurological function
- Neutrophil
ASJC Scopus subject areas
- Neurology
- Medicine(all)
Cite this
Anti-neutrophil antibody enhances the neuroprotective effects of G-CSF by decreasing number of neutrophils in hypoxic ischemic neonatal rat model. / Doycheva, Desislava M.; Hadley, Tiffany; Li, Li; Applegate, Richard Lee; Zhang, John H.; Tang, Jiping.
In: Neurobiology of Disease, Vol. 69, 2014, p. 192-199.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Anti-neutrophil antibody enhances the neuroprotective effects of G-CSF by decreasing number of neutrophils in hypoxic ischemic neonatal rat model
AU - Doycheva, Desislava M.
AU - Hadley, Tiffany
AU - Li, Li
AU - Applegate, Richard Lee
AU - Zhang, John H.
AU - Tang, Jiping
PY - 2014
Y1 - 2014
N2 - Objectives: Neonatal hypoxia ischemia (HI) is an injury that can lead to neurological impairments such as behavioral and learning disabilities. Granulocyte-colony stimulating factor (G-CSF) has been demonstrated to be neuroprotective in ischemic stroke however it has also been shown to induce neutrophilia, ultimately exacerbating neuronal injury. Our hypothesis is that coadministration of anti-neutrophil antibody (Ab) with G-CSF will decrease blood neutrophil counts thereby reducing infarct volume and improving neurological function post HI brain injury. Methods: Rat pups were subjected to unilateral carotid artery ligation followed by 2.5. h of hypoxia. Animals were randomly assigned to five groups: Sham (n = 15), vehicle (HI, n = 15), HI with G-CSF treatment (n = 15), HI with G-CSF + Ab treatment (n = 15), and HI with Ab treatment (n = 15). Ab (325 μg/kg) was administered intraperitoneally while G-CSF (50 μg/kg) was administered subcutaneously 1. h post HI followed by daily injections for 3 consecutive days. Animals were euthanized at 96. h post HI for blood neutrophil counts and brain infarct volume measurements as well as at 5. weeks for neurological function testing and brain weight measurements. Lung and spleen weights at both time points were further analyzed. Results: The G-CSF treatment group showed tendencies to reduce infarct volume and improve neurological function while significantly increasing neutrophil counts. On the other hand, the G-CSF + Ab group significantly reduced infarct volume, improved neurological function and decreased neutrophil counts. The Ab alone group showed reversal of the neuroprotective effects of the G-CSF + Ab group. No significant differences were found in peripheral organ weights between groups. Conclusion: Our data suggest that coadministration of G-CSF with Ab not only prevented brain atrophy but also significantly improved neurological function by decreasing blood neutrophil counts. Hence the neuroprotective effects of G-CSF may be further enhanced if neutrophilia is avoided.
AB - Objectives: Neonatal hypoxia ischemia (HI) is an injury that can lead to neurological impairments such as behavioral and learning disabilities. Granulocyte-colony stimulating factor (G-CSF) has been demonstrated to be neuroprotective in ischemic stroke however it has also been shown to induce neutrophilia, ultimately exacerbating neuronal injury. Our hypothesis is that coadministration of anti-neutrophil antibody (Ab) with G-CSF will decrease blood neutrophil counts thereby reducing infarct volume and improving neurological function post HI brain injury. Methods: Rat pups were subjected to unilateral carotid artery ligation followed by 2.5. h of hypoxia. Animals were randomly assigned to five groups: Sham (n = 15), vehicle (HI, n = 15), HI with G-CSF treatment (n = 15), HI with G-CSF + Ab treatment (n = 15), and HI with Ab treatment (n = 15). Ab (325 μg/kg) was administered intraperitoneally while G-CSF (50 μg/kg) was administered subcutaneously 1. h post HI followed by daily injections for 3 consecutive days. Animals were euthanized at 96. h post HI for blood neutrophil counts and brain infarct volume measurements as well as at 5. weeks for neurological function testing and brain weight measurements. Lung and spleen weights at both time points were further analyzed. Results: The G-CSF treatment group showed tendencies to reduce infarct volume and improve neurological function while significantly increasing neutrophil counts. On the other hand, the G-CSF + Ab group significantly reduced infarct volume, improved neurological function and decreased neutrophil counts. The Ab alone group showed reversal of the neuroprotective effects of the G-CSF + Ab group. No significant differences were found in peripheral organ weights between groups. Conclusion: Our data suggest that coadministration of G-CSF with Ab not only prevented brain atrophy but also significantly improved neurological function by decreasing blood neutrophil counts. Hence the neuroprotective effects of G-CSF may be further enhanced if neutrophilia is avoided.
KW - Anti-neutrophil antibody (Ab)
KW - Granulocyte-colony stimulating factor (G-CSF)
KW - Hypoxia-ischemia (HI)
KW - Neonatal
KW - Neurological function
KW - Neutrophil
UR - http://www.scopus.com/inward/record.url?scp=84902656270&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84902656270&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2014.05.024
DO - 10.1016/j.nbd.2014.05.024
M3 - Article
C2 - 24874543
AN - SCOPUS:84902656270
VL - 69
SP - 192
EP - 199
JO - Neurobiology of Disease
JF - Neurobiology of Disease
SN - 0969-9961
ER -