Effects of minocycline on the expression of NGF and HSP70 and its neuroprotection role following intracerebral hemorrhage in rats

Abstract

The present study was aimed to investigate the effects of minocycline (MC) on the expression of nerve growth factor (NGF) and heat shock protein 70 (HSP70) following intracerebral hemorrhage (ICH) in rats, and explore the neuroprotective function of MC. Seventy-eight male SD rats were randomly assigned to three groups: the ICH control group (n = 36), ICH intervention group (n = 36) and sham operation group (n = 6). The ICH control group and ICH intervention group were subdivided into 6 subgroups at 1, 2, 4, 5, 7 and 14 d after ICH with 6 rats in each subgroup. Type IV collagenase was injected into the basal nuclei to establish the ICH model. All rats showed symptoms of the nervous system after the model was established, and the sympotsm in the ICH control group were more serious than the ICH intervention group. The number of NGF-positive cells and HSP70-positive cells in the ICH intervention group was higher than that of the ICH control group. MC administration by intraperitoneal injection can increase the expression of NGF and HSP70. MC may inhibit the activation of microglia, the inflammatory reaction and factors, matrix metalloproteinases and apoptosis, thus protecting neurons. The change of the expression of NGF and HSP70 may be involved in the pathway of neuroprotection by MC.

Surface functionalization of TiO2 nanotubes with minocycline and its in vitro biological effects on Schwann cells

“…Previous studies indicated that NGF might be related not only to a neuroprotective activity against apoptosis, but also to the formation of new neural pathways, since NGF had the ability to promote neural plasticity and axonal regeneration [ 54 ]. In addition, previous study showed that minocycline treatment increased the number of NGF positive cells in accordance with the result of present study that was the reason of the increasing of gene expression and protein secretory [ 55 ]. The underlying mechanism might be that minocycline could regulate the expression of TrkA, which binds to NGF with high affinity and activates the downstream PI-3K/Akt pathway to inhibit the excessive release of glutamate to reduce brain injury due to Ca 2+ overload, that enhance cell survival and neuronal differentiation [ 55 ].…”

“…In addition, previous study showed that minocycline treatment increased the number of NGF positive cells in accordance with the result of present study that was the reason of the increasing of gene expression and protein secretory [ 55 ]. The underlying mechanism might be that minocycline could regulate the expression of TrkA, which binds to NGF with high affinity and activates the downstream PI-3K/Akt pathway to inhibit the excessive release of glutamate to reduce brain injury due to Ca 2+ overload, that enhance cell survival and neuronal differentiation [ 55 ]. Glial cell-line derived neurotrophic factor (GDNF) belongs to the TGF-β family of neurotrophic factors and plays various and distinct roles in the neuronal signaling pathways.…”

Matrix Metalloproteinases in Acute Intracerebral Hemorrhage

“…Power et al [36] demonstrated that post-ICH in vivo treatment with minocycline significantly reduced brain level of MMP-12, glial activation and apoptosis, and improved neurobehavioral outcomes in rats. Several experimental studies confirmed the role of minocycline administration in reducing BBB damage [84,85], inhibition of microglia activation [86], attenuation of perihematomal edema, neurological deficits, and brain atrophy [87][88][89]. In rat collagenase-induced ICH models, delayed minocycline administration significantly reduced MMP-12 levels, but it is worth to notice that its efficacy was lost and no effects on neuronal loss were observed when treatment was continued for 7 days [90].…”

Central Nervous System Tissue Regeneration after Intracerebral Hemorrhage: The Next Frontier

“…In autologous blood induced ICH rats, administration of minocycline facilitates an "M2"-like polarization and increases microglia-derived BDNF; enhanced neurogenesis is observed with more DCX and Tuj-1 positive neuron-like cells than in a control group at 24 h after ICH onset [144]. Another study reported NGF elevation by minocycline after collagenase ICH [145]. However, minocycline injection is documented to inhibit angiogenesis by downregulating the level of VEGF and its receptors after experimental ICH, which may hinder tissue regeneration in the late phase [146].…”