Ovarian Damages Produced by Aerosolized Fine Particulate Matter (PM2.5) Pollution in Mice: Possible Protective Medications and Mechanisms.

BACKGROUND: Ambient aerosol fine particulate matter (PM2.5) is associated with male reproductive toxicity in experiments and may have adverse effects in the female. However, studies evaluating the protective effects and precise mechanisms of aspirin, Vitamin C, Vitamin E, or ozone against toxic effects of PM2.5are sparse. This study was conducted to investigate the possible protective effects and mechanisms of aspirin, Vitamin C, Vitamin E, or ozone on fertility in female mice treated with PM2.5. METHODS: Eighty-four ICR mice were divided into six groups: control group, PM2.5group, PM2.5 + aspirin group, PM2.5 + Vitamin C group, PM2.5 + Vitamin E group, and PM2.5 + ozone group. PM2.5was given by intratracheal instillation every 2 days for 3 weeks. Aspirin, Vitamin C, and Vitamin E were given once a day by oral gavage for 3 weeks, and ozone was administered by intraperitoneal injection once a day for 3 weeks. The levels of anti-Müllerian hormone (AMH), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured using enzyme-linked immunosorbent assay. Western blotting analysis was used to analyze the expressions of Bcl-2, Bax, and caspase-3 in ovaries. Changes in histological structure were examined by light microscope and electron microscopy was used to detect ultramicrostructure. RESULTS: The results demonstrated that PM2.5 decreased AMH levels (P < 0.001); however, aspirin (P < 0.001), Vitamin C (P < 0.001), Vitamin E (P = 0.001), and ozone (P = 0.002) alleviated the decrease. Changes of IL-6, TNF-α, 8-OHdG, Bax/Bcl-2, and caspase-3 in PM2.5group were increased compared to control group (P < 0.001), while in PM2.5 + aspirin, PM2.5 + Vitamin C, PM2.5 + Vitamin E, and PM2.5 + ozone groups, they were statistically decreased compared to PM2.5group (P < 0.001 or P< 0.05). CONCLUSIONS: PM2.5cause the damage of ovaries, and aspirin, Vitamin C, Vitamin E, and ozone antagonizes the damage. The protective mechanism is probably due to its ability to blunt the inflammatory and oxidative stress caused by PM2.5, which subsequently suppressing the expression of apoptotic regulatory protein and reducing the incidence of ovary apoptosis.

Analgesic Effects and Neuropathology Changes of Electroacupuncture on Curing a Rat Model of Brachial Plexus Neuralgia Induced by Cobra Venom.

BACKGROUND: Electroacupuncture (EA) is widely applied to treat neuropathic pain. Brachial plexus neuralgia (BPN) is a common form of chronic persistent pain. Few studies have evaluated the analgesic effects and mechanism of EA using the novel animal model of BPN. OBJECTIVE: To observe the curative effects of repeated EA on curing BPN induced by administration of cobra venom to the lower trunk of the right brachial plexus. STUDY DESIGN: Controlled animal study. SETTING: Department of Anesthesiology, Pain Medicine & Critical Care Medicine, Aviation General Hospital of China Medical University. METHODS: Sixty-six adult male Sprague-Dawley rats were equally and randomly divided into the following groups: normal control (NC), brachial plexus neuralgia (BPN), BPN with sham EA stimulation, BPN with EA stimulation starting on postoperative day 1 (EA1), and BPN with EA stimulation starting on postoperative day 12 (EA12). The BPN model was established by administration of cobra venom to the lower trunk of the right brachial plexus. On postoperative day 1 or day 12, EA (constant aquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1 - 1.5 - 2 mA) was applied to the right "Shousanli" (LI10) and "Quchi" (LI11) acupoints for 30 minutes, once every other day for 12 times in both groups. Mechanical withdrawal thresholds (MWT) were tested with von Frey filaments. Video recordings were conducted to analyze the spontaneous exploratory behaviors. Moreover, the organizational and structural alterations of the right brachial plexus and cervical cord (C8-T1) were examined via light and electron microscopy. RESULTS: Following the production of the BPN model, the MWT of both ipsilateral and contralateral paws demonstrated a profound decrease (P < 0.05). But after EA interventions, the MWT showed a significant increase (P < 0.05). In comparison to the EA12 group, the analgesic effects of the EA1 group were more significant, and similar results were observed in exploratory behaviors. However, grooming behaviors did not demonstrate significant differences. Meanwhile, on day 12 after surgery it was observed under light microscopy that the inflammatory response in the right brachial plexus and cervical cord (C8-T1) were significantly attenuated after EA stimulation. Furthermore, the demyelination of the brachial plexus and cervical cord (C8-T1) were also reversed. LIMITATIONS: Limitations include the fact that there was demyelination of the cervical cord (C8-T1) in the control group because of inappropriate manipulation. CONCLUSION: Repeated EA contributes significant analgesic effects in the treatment of BPN.

Trigeminal neuralgia induced by cobra venom in the rat leads to deficits in abilities of spatial learning and memory.

BACKGROUND: Patients with chronic pain usually suffer from cognitive impairment, with memory deterioration being the most common deficit that affects daily functioning and quality of life. The causes for this impairment are not clear despite intensive clinical studies. Few studies have evaluated impaired learning using animal models of persistent pain. OBJECTIVE: In this study, a new trigeminal neuralgia model induced by cobra venom was adopted to explore effects of chronic pain on spatial learning and memory in rats. STUDY DESIGN: Controlled animal study. SETTING: Department of Anesthesiology, Pain Medicine & Critical Care Medicine, Aviation General Hospital of China Medical University. METHODS: Thirty adult male Sprague-Dawley rats were randomly divided into 2 groups (n = 15): NS control group and cobra venom group, 0.9% sterile saline or cobra venom solution was injected into the sheath of the infraorbital nerve (ION), respectively. The development of trigeminal neuralgia was accessed by changes in free behavioral activity 3 days before the surgery and 3, 7, 12, 20, and 30 days after the surgery to identify whether the model was successful or not. Morris water maze test determined the abilities of spatial learning and memory at the time points before the surgery, and 2 weeks and 5 weeks after the surgery. We also observed the ultrastructure of the ION and medulla oblongata of rats following 8 weeks of chronic trigeminal neuropathic pain. RESULTS: Rats with the cobra venom injection displayed significantly more face grooming and fewer exploratory activities compared to the NS control group or baseline (P < 0.01). Both groups improved their latency to reach the platform with the largest difference on the first day (P < 0.01), but without memory deficits in a probe trial for the second water maze protocol. For the third water maze testing, the rats in the cobra venom group experienced decreased abilities of spatial learning and memory, a longer latency with spatial memory deficits during the probe trial (P < 0.05). At the ultrastructural level, we found changes in the medulla oblongata after cobra venom injection resulting in severe demyelination and loss of axons that might be implicated in the causes of cognitive deficits. LIMITATIONS: Limitations include partial vision loss in the eye on the lesion side of the rats that might be missed and the absence of evaluating the ultrastructural changes in other parts of the brain. CONCLUSIONS: The results of this study suggest that trigeminal neuralgia induced by cobra venom in adult rats can impair spatial learning and memory function over time and results in demonstrable changes in the ultrastructure of the medulla oblongata. This new animal model may be useful for future studies on the effect of chronic pain on learning and cognition.

A new animal model of trigeminal neuralgia produced by administration of cobra venom to the infraorbital nerve in the rat.

BACKGROUND: Understanding the mechanism of trigeminal neuralgia may be elucidated by developing laboratory animal models that closely mimic the features of this specific type of neuropathic pain. We have developed an experimental animal model for trigeminal neuralgia using a technique of injecting cobra venom into the infraorbital nerve (ION) trunk. METHODS: Male Sprague-Dawley rats were subjected to the administration of cobra venom or saline into the ION trunk. Mechanical stimuli were applied to the ION territory in consecutive days after surgery. Mechanical thresholds were measured over a 90-day period on the bilateral facial region. Vascular permeability in the ION territory was measured using Evans blue dye. RESULTS: The cobra venom-treated rats developed mechanical allodynia 3 days after surgery that lasted for 60 days postoperatively at the ipsilateral side. The mechanical thresholds of the contralateral ION territory also showed a profound decrease but were sustained for only approximately 30 days. There was no change of mechanical thresholds in the control groups. The extravasation of Evans blue increased significantly in the skin after administration of cobra venom to the ION compared with control rats (P < 0.05). CONCLUSION: The cobra venom model may provide a reasonable model for investigating the mechanism of trigeminal neuropathic pain.