Investigation of macrophage polarization in herniated nucleus pulposus of patients with lumbar intervertebral disc herniation.

Macrophage infiltration and polarization during lumbar intervertebral disc herniation (LDH) have attracted increased attention but their role remains unclear. To explore macrophage polarization in herniated nucleus pulposus (NP) tissue of patients with LDH and investigate the association between cell frequency and different clinical characteristics or symptoms, we conducted a retrospective study by analyzing NP tissue samples from 79 patients. Clinical features and symptoms, using the visual analog scale (VAS) and Oswestry disability index (ODI), were collected. The macrophage markers CD68, CCR7, CD163, and CD206; pro-inflammatory cytokine TNF-α; and anti-inflammatory factor IL-4 were analyzed by immunohistochemistry. The frequency of polarized macrophages and positivity rate of pro- and anti-inflammatory cytokines showed significant differences in some of clinical characteristics. Specifically, higher CCR7+ and TNF-α + proportions were identified in the high-intensity zone (HIZ) and the type of extrusion and sequestration NP tissue than in non-HIZ and protrude NP tissue. Higher CD206+ and IL-4+ proportion were detected in Modic changes. However, no differences in gender, age, smoking status, Pfirrmann grade, analgesic use, leg pain duration, and segments were found between groups. CD68+ , CCR7+ , and CD206+ cell proportions, and TNF-α and IL-4 showed positive associations with VAS scores preoperation. Associations between ODI and the macrophages markers were weak/insignificant. Our results indicated that macrophage polarization or macrophage-like cells contribute to LDH pathological features. Macrophage populations displaying significant associations with VAS score reflected continuous M1/M2 transition contributing to pain during LDH. These findings may contribute to enhanced/personalized pharmacological interventions for patients with LDH considering pain heterogeneity.

Ligustrazine monomer against cerebral ischemia/reperfusion injury.

Ligustrazine (2,3,5,6-tetramethylpyrazine) is a major active ingredient of the Szechwan lovage rhizome and is extensively used in treatment of ischemic cerebrovascular disease. The mechanism of action of ligustrazine use against ischemic cerebrovascular diseases remains unclear at present. This study summarizes its protective effect, the optimum time window of administration, and the most effective mode of administration for clinical treatment of cerebral ischemia/reperfusion injury. We examine the effects of ligustrazine on suppressing excitatory amino acid release, promoting migration, differentiation and proliferation of endogenous neural stem cells. We also looked at its effects on angiogenesis and how it inhibits thrombosis, the inflammatory response, and apoptosis after cerebral ischemia. We consider that ligustrazine gives noticeable protection from cerebral ischemia/reperfusion injury. The time window of ligustrazine administration is limited. The protective effect and time window of a series of derivative monomers of ligustrazine such as 2-[(1,1-dimethylethyl)oxidoimino]methyl]-3,5,6-trimethylpyrazine, CXC137 and CXC195 after cerebral ischemia were better than ligustrazine.

[Expressions of GAP43, P38 mRNA and protein in insular electrical kindled rats and its significance].

OBJECTIVE: To investigate the expression of neural growth-associated protein (GAP-43) and synaptophysin (P38) gene and protein in insular electrical kindled epileptic rats and its significance. METHODS: Seventy-two male adult rats were divided into kindled group (n = 36) and sham group (n = 36) randomly. Each group was further divided into 1, 3, 7, 15, 30 and 60 d sub-groups (n = 6) respectively. After kindling with immunohistochemical staining and hybridization in situ, the altered expressions of GAP-43 and P38 were detected in hippocampus of insular electrical kindled epilepsy rats. RESULTS: Epilepsy day 1: GAP-43 mRNA and protein expression at hippocampus dentate gyrus granular cell layer, hilus and CA3 pyramidal layer in the kindled group were higher than the sham group (P < 0.05). The expressions declined at Day 3 (P > 0.05). Expressions became elevated again at Day 7 and they were significantly higher than those in the sham group at Days 15 and 30 (P < 0.05). There was no statistical difference between two groups at Day 60 (P > 0.05). Expressions of P38 mRNA and protein: hybridization signal and immunostaining at hippocampus dentate gyrus granular cell layer, hilus and CA3 pyramidal layer began to rise at Day 7 and peaked at Day 15 (P < 0.01). They lasted 4 weeks and then began to decline. CONCLUSION: Insular epilepsy is closely related with temporal hippocampus. GAP-43 and P38 may be the pathological basis of insular epilepsy and the key molecular mechanism of synaptic plasticity.