1.Effect of Macrophage Migration Inhibitory Factor on Corneal Sensitivity after Laser In Situ Keratomileusis in Rabbit.
Joon Young HYON ; Stacey HOSE ; Celine GONGORA ; Debasish SINHA ; Terrence O'BRIEN
Korean Journal of Ophthalmology 2014;28(2):170-176
PURPOSE: To investigate the effect of macrophage migration inhibitory factor (MIF) on corneal sensitivity after laser in situ keratomileusis (LASIK) surgery. METHODS: New Zealand white rabbits were used in this study. A hinged corneal flap (160-microm thick) was created with a microkeratome, and -3.0 diopter excimer laser ablation was performed. Expressions of MIF mRNA in the corneal epithelial cells and surrounding inflammatory cells were analyzed using reverse transcription polymerase chain reaction at 48 hours after LASIK. After LASIK surgery, the rabbits were topically given either 1) a balanced salt solution (BSS), 2) MIF (100 ng/mL) alone, or 3) a combination of nerve growth factor (NGF, 100 ug/mL), neurotrophine-3 (NT-3, 100 ng/mL), interleukin-6 (IL-6, 5 ng/mL), and leukemia inhibitory factor (LIF, 5 ng/mL) four times a day for three days. Preoperative and postoperative corneal sensitivity at two weeks and at 10 weeks were assessed using the Cochet-Bonnet esthesiometer. RESULTS: Expression of MIF mRNA was 2.5-fold upregulated in the corneal epithelium and 1.5-fold upregulated in the surrounding inflammatory cells as compared with the control eyes. Preoperative baseline corneal sensitivity was 40.56 +/- 2.36 mm. At two weeks after LASIK, corneal sensitivity was 9.17 +/- 5.57 mm in the BSS treated group, 21.92 +/- 2.44 mm in the MIF treated group, and 22.42 +/- 1.59 mm in the neuronal growth factors-treated group (MIF vs. BSS, p < 0.0001; neuronal growth factors vs. BSS, p < 0.0001; MIF vs. neuronal growth factors, p = 0.815). At 10 weeks after LASIK, corneal sensitivity was 15.00 +/- 9.65, 35.00 +/- 5.48, and 29.58 +/- 4.31 mm respectively (MIF vs. BSS, p = 0.0001; neuronal growth factors vs. BSS, p = 0.002; MIF vs. neuronal growth factors, p = 0.192). Treatment with MIF alone could achieve as much of an effect on recovery of corneal sensation as treatment with combination of NGF, NT-3, IL-6, and LIF. CONCLUSIONS: Topically administered MIF plays a significant role in the early recovery of corneal sensitivity after LASIK in the experimental animal model.
Animals
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Epithelium, Corneal/*drug effects/innervation/physiology
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Female
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Humans
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Interleukin-6/pharmacology
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Keratomileusis, Laser In Situ/*methods
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Leukemia Inhibitory Factor/pharmacology
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Macrophage Migration-Inhibitory Factors/genetics/*pharmacology
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Models, Animal
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Nerve Growth Factor/pharmacology
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Nerve Regeneration/*drug effects/physiology
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Neurotrophin 3/pharmacology
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RNA, Messenger/metabolism
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Rabbits
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Recovery of Function/*drug effects/physiology
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Sensation/*drug effects/physiology
2.Study on functional recovery of hypoxic-ischemic brain injury by Rg1-induced NSCs.
Yingbo LI ; Liu TU ; Di CHEN ; Rong JIANG ; Yaping WANG ; Shall WANG
China Journal of Chinese Materia Medica 2012;37(4):509-514
OBJECTIVETo observe the effect of Rg1-induced NSCs in treatment of neonatal rat model with hypoxiaischemia.
METHODThe neonatal rat model of HIE was established and assessed by using TTC staining and behavioral observation, then Rg1-induced NSCs was transplanted into the neonatal rat of HIE by lateral ventricle injection. Water maze test and somatosensory evoked potential were detected to observe brain function and the immunohistochemistry was done to assess growth and differentiation about transplanted NSCs a month after transplanted.
RESULTThe transplantation of Rg1-induced NSCs could significantly shorten incubation period, swimming distance, exploration time of target quadrants of water maze test and incubation period and amplitude of somatosensory evoked potentials. Additionally, the concentrated expression appeared in the hippocampus and grew around the ischemic injury area in transplantation group.
CONCLUSIONTransplantation of Rg1-induced NSCs play a better role in the treatment of neonatal HIE rats.
Animals ; Cell Differentiation ; drug effects ; Evoked Potentials ; Female ; Ginsenosides ; pharmacology ; Hippocampus ; pathology ; physiopathology ; Hypoxia-Ischemia, Brain ; pathology ; physiopathology ; therapy ; Male ; Maze Learning ; Neural Stem Cells ; cytology ; drug effects ; transplantation ; Rats ; Rats, Sprague-Dawley ; Recovery of Function ; physiology
3.Combined therapy of methylprednisolone and brain-derived neurotrophic factor promotes axonal regeneration and functional recovery after spinal cord injury in rats.
Lixin LI ; Qiwu XU ; Youzhang WU ; Weixing HU ; Peiyuan GU ; Zhen FU
Chinese Medical Journal 2003;116(3):414-418
OBJECTIVETo investigate the effects of combination therapy with methylprednisolone (MP) and brain-derived neurotrophic factor (BDNF) on axonal remyelination and functional recovery after spinal cord injury in rats.
METHODSForty-five rats were randomly divided into three groups: Group A received MP and BDNF; group B received MP and cerebrospinal fluid (CSF); and group C received CSF only. Contusion injury to adult rat spinal cord was produced at the T(10) vertebra level followed by immediate intravenous MP or CSF, and was thereafter infused intrathecally with BDNF or CSF for 6 weeks. Axonal remyelination and functional recovery was observed using RT-PCR, immunohistochemistry and open field locomotion.
RESULTSAn increase of 28.4% +/- 2.3% in the expression of proteolipid protein (PLP) gene, an endogenous indicator of axonal remyelination, was demonstrated in group A 24 hours after injury. Ten weeks later, there were significant decreases in hematogenous inflammatory cellular infiltration in groups A and B compared to C (P < 0.05). Concomitantly, a significant amount of axonal remyelination was observed in group A compared to groups B and C (P < 0.05). Furthermore, combination therapy using MP and BDNF in group A resulted in stimulation of hindlimb activity as well as improvement in the rate of functional recovery in open field locomotion (P < 0.05).
CONCLUSIONSCombined therapy of MP and BDNF can improve functional recovery through mechanisms that include attenuating inflammatory cellular infiltration and enhancing axonal remyelination at the injury site. Such a combination may be an effective approach for treatment of spinal cord injury.
Animals ; Axons ; physiology ; Brain-Derived Neurotrophic Factor ; administration & dosage ; Drug Therapy, Combination ; Female ; Methylprednisolone ; administration & dosage ; Myelin Proteolipid Protein ; genetics ; Nerve Regeneration ; drug effects ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Recovery of Function ; Spinal Cord Injuries ; drug therapy ; metabolism ; physiopathology
4.No spatial memory deficit exists in Kunming mice that recently recovered from motor defects following 3-nitropropionic acid intoxication.
Xiao-Min LI ; Bing-Gen ZHU ; Jian-Bo NI ; Chun-Yan CAO ; Jie-Ping ZHANG ; Xu-Dong ZHAO ; Rong-Shen ZHU
Neuroscience Bulletin 2009;25(2):87-93
OBJECTIVENumerous studies have described both motor defects and cognitive impairments in several strains of rodents following 3-nitropropionic acid (3-NP) intoxication. In the present study, we investigated spatial recognition memory in Kunming mice that just recovered from motor defects induced by 3-NP.
METHODSMouse model was made by systemic subacute 3-NP treatment, and spatial recognition memory was measured through the Y-maze Test, a simple two-trial recognition test.
RESULTS(1) On day 15 following 3-NP treatment, affected Kunming mice did not show motor defects in the Rotarod test and presented normal gait again. (2) In the following Y-maze test after 1h interval, the percentage (90.0%) of mice showing novel arm preference in 3-NP treatment group was significantly higher than the random chance level (50%), although it was only slightly higher than that (83.3%) in control group. On day 45 after 3-NP treatment, mice failed to choose unfamiliar novel arm as first choice, and the same occured in the control group. (3) For both post-intoxicated (on day 15 and day 45 following 3-NP treatment) and control groups, the duration in the novel arm and the frequency of entering it, were longer and higher compared with familiar start and other arms. For these mice that recently recovered from motor defects following 3-NP intoxication, no spatial memory deficits were observed through Y-maze Test.
CONCLUSIONKunming mice used in our assays might possess resistance to cognitive impairment induced by 3-NP, which is consistent with previous findings in Swiss EPM-M1 mice.
Animals ; Behavior, Animal ; Convulsants ; toxicity ; Male ; Maze Learning ; drug effects ; Memory Disorders ; etiology ; Mice ; Mice, Inbred Strains ; Motor Activity ; drug effects ; Movement Disorders ; etiology ; Nitro Compounds ; toxicity ; Poisoning ; complications ; etiology ; Propionates ; toxicity ; Recovery of Function ; drug effects ; physiology ; Rotarod Performance Test ; Time Factors
5.Effectiveness of Subacromial Anti-Adhesive Agent Injection after Arthroscopic Rotator Cuff Repair: Prospective Randomized Comparison Study.
Chung Hee OH ; Joo Han OH ; Sae Hoon KIM ; Jae Hwan CHO ; Jong Pil YOON ; Joon Yub KIM
Clinics in Orthopedic Surgery 2011;3(1):55-61
BACKGROUND: Arthroscopic rotator cuff repair generally has a good clinical outcome but shoulder stiffness after surgery due to subacromial adhesion is one of the most common and clinically important complications. Sodium hyaluronate (HA) has been reported to be an anti-adhesive agent in a range of surgical procedures. However, there are few reports of the outcomes of arthroscopic rotator cuff repair of the shoulder. This study examined whether a subacromial injection of HA/carboxymethylated cellulose (CMC) affected the postoperative shoulder stiffness and healing of rotator cuff repair, as well as the safety of an injection. METHODS: Between January 2008 and May 2008, 80 consecutive patients with arthroscopic rotator cuff repair were enrolled. The patients were assigned randomly to the HA/CMC injection group (n = 40) or control group (n = 40). All patients were evaluated using the visual analog scale (VAS) for pain, passive range of motion at 2, 6 weeks, 3, 6, 12 months after surgery, and the functional scores at 6, 12 months postoperatively. Cuff healing was also evaluated using CT arthrography or ultrasonography at 6 or 12 months after surgery. RESULTS: The HA/CMC injection group showed faster recovery of forward flexion at 2 weeks postoperatively than the control group but the difference was not statistically significant (p = 0.09). There were no significant difference in pain VAS, internal rotation, external rotation and functional scores between two groups at each follow-up period. The functional scores improved 6 months after surgery in both groups but there were no differences between the two groups. The incidence of unhealed rotator cuff was similar in the two groups. There were no complications related to an injection of anti-adhesive agents including wound problems or infections. CONCLUSIONS: A subacromial injection of an anti-adhesive agent after arthroscopic rotator cuff repair tended to produce faster recovery in forward flexion with no adverse effects on cuff healing. However, its anti-adhesive effects after rotator cuff repair should be considered carefully with further studies.
Adult
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Aged
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Arthroscopy/*adverse effects/*methods
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Carboxymethylcellulose Sodium
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Drug Carriers
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Female
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Humans
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Hyaluronic Acid/adverse effects/*therapeutic use
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Male
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Middle Aged
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Pain
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Prospective Studies
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Range of Motion, Articular
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Recovery of Function
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Rotator Cuff/injuries/*surgery
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Shoulder Joint/physiology
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Tissue Adhesions/*prevention & control
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Treatment Outcome
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Viscosupplements/adverse effects/*therapeutic use
6.Protective effect of liposome-mediated glial cell line-derived neurotrophic factor gene transfer in vivo on motoneurons following spinal cord injury in rats.
Kai-Wu LU ; Zhe-Yu CHEN ; Tie-Sheng HOU
Chinese Journal of Traumatology 2004;7(5):275-279
OBJECTIVETo investigate the effect of liposome-mediated glial cell line-derived neurotrophic factor (GDNF) gene transfer in vivo on spinal cord motoneurons after spinal cord injury (SCI) in adult rats.
METHODSSixty male Sprague-Dawley rats were divided equally into two groups: GDNF group and control group. The SCI model was established according to the method of Nystrom, and then the DC-Chol liposomes and recombinant plasmid pEGFP-GDNF cDNA complexes were injected into the injured spinal cord. The expression of GDNF cDNA 1 week after injection was detected by RT-PCR and fluorescence microscope. We observed the remaining motoneurons in the anterior horn and the changes of cholinesterase (CHE) and acid phosphatase (ACP) activity using Nissl and enzyme histochemistry staining. The locomotion function of hind limbs of rats was evaluated using inclined plane test and BBB locomotor scale.
RESULTSRT-PCR and fluorescence observation confirmed the presence of expression of GDNF cDNA 1 week and 4 weeks after injection. At 1, 2, 4 weeks after SCI, the number of motoneurons in the anterior horn in GDNF group (20.4+/-3.2, 21.7+/-3.6, 22.5+/-3.4) was more than that in control group (16.8+/-2.8, 17.3+/-2.7, 18.2+/-3.2, P<0.05). At 1, 2 weeks after SCI, the mean gray of the CHE-stained spinal motoneurons in GDNF group (74.2+/-25.8, 98.7+/-31.6) was less than that in control group (98.5+/-32.2, 134.6+/-45.2, P<0.01), and the mean gray of ACP in GDNF group (84.5+/-32.6, 79.5+/-28.4) was more than that in control group (61.2+/-24.9, 52.6+/-19.9, P<0.01). The locomotion functional scales in GDNF group were higher than that in control group within 1 to 4 weeks after SCI (P<0.05).
CONCLUSIONSGDNF gene transfer in vivo can protect motoneurons from death and degeneration induced by incomplete spinal cord injury as well as enhance locomotion functional restoration of hind limbs. These results suggest that liposome-mediated delivery of GDNF cDNA might be a practical method for treating traumatic spinal cord injury.
Animals ; Disease Models, Animal ; Gene Transfer Techniques ; Glial Cell Line-Derived Neurotrophic Factor ; Injections, Intralesional ; Liposomes ; Locomotion ; physiology ; Male ; Motor Neurons ; drug effects ; Nerve Growth Factors ; pharmacology ; Nerve Regeneration ; physiology ; Neuroprotective Agents ; pharmacology ; Primary Prevention ; methods ; Probability ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Recovery of Function ; Reference Values ; Reverse Transcriptase Polymerase Chain Reaction ; Spinal Cord Injuries ; pathology ; prevention & control ; therapy