1.Comprehensive therapeutics targeting the corticospinal tract following spinal cord injury.
An-Kai XU ; Zhe GONG ; Yu-Zhe HE ; Kai-Shun XIA ; Hui-Min TAO
Journal of Zhejiang University. Science. B 2019;20(3):205-218
Spinal cord injury (SCI), which is much in the public eye, is still a refractory disease compromising the well-being of both patients and society. In spite of there being many methods dealing with the lesion, there is still a deficiency in comprehensive strategies covering all facets of this damage. Further, we should also mention the structure called the corticospinal tract (CST) which plays a crucial role in the motor responses of organisms, and it will be the focal point of our attention. In this review, we discuss a variety of strategies targeting different dimensions following SCI and some treatments that are especially efficacious to the CST are emphasized. Over recent decades, researchers have developed many effective tactics involving five approaches: (1) tackle more extensive regions; (2) provide a regenerative microenvironment; (3) provide a glial microenvironment; (4) transplantation; and (5) other auxiliary methods, for instance, rehabilitation training and electrical stimulation. We review the basic knowledge on this disease and correlative treatments. In addition, some well-formulated perspectives and hypotheses have been delineated. We emphasize that such a multifaceted problem needs combinatorial approaches, and we analyze some discrepancies in past studies. Finally, for the future, we present numerous brand-new latent tactics which have great promise for curbing SCI.
Animals
;
Astrocytes/cytology*
;
Axons/physiology*
;
Cell Transplantation
;
Disease Models, Animal
;
Electric Stimulation
;
Humans
;
Microglia/cytology*
;
Motor Neurons/cytology*
;
Nerve Regeneration
;
Neuroglia/cytology*
;
Neuronal Plasticity
;
Neurons/cytology*
;
Oligodendroglia/cytology*
;
Pyramidal Tracts/pathology*
;
Recovery of Function
;
Regenerative Medicine/methods*
;
Spinal Cord Injuries/therapy*
2.Analysis of 4 Cases of Electrocution due to Direct Current Electronic Hunter.
Long Long ZHU ; Fang TONG ; Yue LIANG ; Ten Zin LOPSONG ; Wei Sheng HUANG ; Yu Luo LIU ; Yi Wu ZHOU
Journal of Forensic Medicine 2019;35(5):592-595
Objective To summarize the characteristics of cases of electrocution due to direct current (DC) electronic hunter, and to provide references for forensic identification. Methods Four cases of electrocution due to DC electronic hunter were collected. Statistical analysis was carried out from the perspective of the scene and electric marks distribution, damage characteristics and histopathological changes. Results All the 4 cases of electrocution were accidental events. There were multiple electric marks, most of which were located in the lower limbs with serious damage. Some strip type electric marks were visible. Conclusion The distribution, morphological characteristics and severity of the electric marks caused by DC electronic hunter are different from those of the ordinary low-voltage alternating current damage. It is alerting that there would be actions of destroying the scene and abandoning the corpse in such cases.
Cadaver
;
Electric Injuries/pathology*
;
Electricity/adverse effects*
;
Fatal Outcome
;
Forensic Pathology/methods*
;
Humans
;
Lower Extremity
3.The effects of single versus combined therapy using LIM-kinase 2 inhibitor and type 5 phosphodiesterase inhibitor on erectile function in a rat model of cavernous nerve injury-induced erectile dysfunction.
Min Chul CHO ; Junghoon LEE ; Juhyun PARK ; Sohee OH ; Ji Sun CHAI ; Hwancheol SON ; Jae-Seung PAICK ; Soo Woong KIM
Asian Journal of Andrology 2019;21(5):493-500
We aimed to determine whether combination of LIM-kinase 2 inhibitor (LIMK2i) and phosphodiesterase type-5 inhibitor (PDE5i) could restore erectile function through suppressing cavernous fibrosis and improving cavernous apoptosis in a rat model of cavernous nerve crush injury (CNCI). Seventy 12-week-old Sprague-Dawley rats were equally distributed into five groups as follows: (1) sham surgery (Group S), (2) CNCI (Group I), (3) CNCI treated with daily intraperitoneal administration of 10.0 mg kg-1 LIMK2i (Group I + L), (4) daily oral administration of 20.0 mg kg-1 udenafil, PDE5i (Group I + U), and (5) combined administration of 10.0 mg kg-1 LIMK2i and 20.0 mg kg-1 udenafil (Group I + L + U). Rats in Groups I + L, I + U, and I + L + U were treated with respective regimens for 2 weeks after CNCI. At 2 weeks after surgery, erectile response was assessed using electrostimulation. Penile tissues were processed for histological studies and western blot. Group I showed lower intracavernous pressure (ICP)/mean arterial pressure (MAP), lower area under the curve (AUC)/MAP, decreased immunohistochemical staining for alpha-smooth muscle (SM) actin, higher apoptotic index, lower SM/collagen ratio, increased phospho-LIMK2-positive fibroblasts, decreased protein kinase B/endothelial nitric oxide synthase (Akt/eNOS) phosphorylation, increased LIMK2/cofilin phosphorylation, and increased protein expression of fibronectin, compared to Group S. In all three treatment groups, erectile responses, protein expression of fibronectin, and SM/collagen ratio were improved. Group I + L + U showed greater improvement in erectile response than Group I + L. SM content and apoptotic index in Groups I + U and I + L + U were improved compared to those in Group I. However, Group I + L did not show a significant improvement in SM content or apoptotic index. The number of phospho-LIMK2-positive fibroblasts was normalized in Groups I + L and I + L + U, but not in Group I + U. Akt/eNOS phosphorylation was improved in Groups I + U and I + L + U, but not in Group I + L. LIMK2/cofilin phosphorylation was improved in Groups I + L and I + L + U, but not in Group I + U. Our data indicate that combined treatment of LIMK2i and PDE5i immediate after CN injury could improve erectile function by improving cavernous apoptosis or eNOS phosphorylation and suppressing cavernous fibrosis. Rectification of Akt/eNOS and LIMK2/cofilin pathways appears to be involved in their improvement.
Animals
;
Apoptosis/drug effects*
;
Arterial Pressure
;
Electric Stimulation
;
Erectile Dysfunction/pathology*
;
Lim Kinases/antagonists & inhibitors*
;
Male
;
Nerve Crush
;
Nitric Oxide Synthase Type III/metabolism*
;
Penis/pathology*
;
Peripheral Nerve Injuries/pathology*
;
Phosphodiesterase 5 Inhibitors/therapeutic use*
;
Phosphorylation
;
Pyrimidines/therapeutic use*
;
Rats
;
Rats, Sprague-Dawley
;
Sulfonamides/therapeutic use*
4.Role of Jun amino-terminal kinase (JNK) in apoptosis of cavernosal tissue during acute phase after cavernosal nerve injury.
Won Hoon SONG ; Hwancheol SON ; Soo Woong KIM ; Jae-Seung PAICK ; Min Chul CHO
Asian Journal of Andrology 2018;20(1):50-55
The present study aimed to identify which mitogen-activated protein kinase (p38 or Jun amino-terminal kinase [JNK]) was involved in cavernosal apoptosis during the acute phase after cavernosal nerve crush injury (CNCI) in rats to ameliorate apoptosis of cavernosal tissue, such as smooth muscle (SM). A total of twenty 10-week-old male Sprague-Dawley rats were divided equally into two groups: sham surgery (S) and CNCI (I). The I group approximated the clinical situation of men undergoing radical prostatectomy using two 60-second compressions of both CNs with a microsurgical vascular clamp. At 2-week postinjury, erectile response was assessed using electrostimulation. Penile tissues were harvested for immunohistochemistry analysis of alpha-SM actin (α-SMA), western blot analysis, and double immunofluorescence analysis of α-SMA and phosphorylated p38 or JNK, as well as double immunofluorescent of TUNEL and phosphorylated p38 or JNK. At 2-week postinjury, the I group had a significantly lower intracavernous pressure (ICP)/mean arterial pressure (MAP) and a lower area under the curve (AUC)/MAP than the S group. The I group also exhibited decreased immunohistochemical staining of α-SMA, an increase in the number of SM cells positive for phosphorylated JNK, an increased number of apoptotic cells positive for phosphorylated JNK, and increased JNK phosphorylation compared with the S group. However, there was no significant difference in p38 phosphorylation expression or the number of SM cells positive for phosphorylated p38 between the two groups. In conclusion, our data suggest that JNK, not p38, is involved in cavernosal apoptosis during the acute phase after partial CN damage.
Animals
;
Apoptosis
;
Disease Models, Animal
;
Electric Stimulation
;
MAP Kinase Kinase 4/metabolism*
;
Male
;
Penile Erection
;
Penis/pathology*
;
Peripheral Nerve Injuries/pathology*
;
Phosphorylation
;
Prostatectomy
;
Rats
;
Rats, Sprague-Dawley
;
Signal Transduction
;
p38 Mitogen-Activated Protein Kinases/metabolism*
5.Role of inhibiting LIM-kinase2 in improving erectile function through suppression of corporal fibrosis in a rat model of cavernous nerve injury.
Juhyun PARK ; Sung Yong CHO ; Kwanjin PARK ; Ji Sun CHAI ; Hwancheol SON ; Soo Woong KIM ; Jae-Seung PAICK ; Min Chul CHO
Asian Journal of Andrology 2018;20(4):372-378
We evaluated whether LIM-kinase 2 inhibitor (LIMK2i) could improve erectile function by suppressing corporal fibrosis through the normalization of the Rho-associated coiled-coil protein kinase 1 (ROCK1)/LIMK2/Cofilin pathway in a rat model of cavernous nerve crush injury (CNCI). Sixty 11-week-old male Sprague-Dawley rats were divided equally into five groups: sham surgery (S), CNCI (I), and CNCI treated with low-dose (L), medium-dose (M), and high-dose (H) LIMK2i. The L, M, and H groups were treated with a daily intraperitoneal injection of LIMK2i (2.5, 5.0, and 10.0 mg kg-1 body weight, respectively) for 1 week after surgery. The erectile response was assessed using electrostimulation at 1 week, postoperatively. Penile tissues were processed for Masson's trichrome staining, double immunofluorescence, and Western blot assay. Erectile responses in the H group improved compared with the I group, while the M group showed only partial improvement. A significantly decreased smooth muscle/collagen ratio and an increased content of fibroblasts positive for phospho-LIMK2 were noted in the I group. The M and H groups revealed significant improvements in histological alterations and the dysregulated LIMK2/Cofilin pathway, except for LIMK2 phosphorylation in the M group. The inhibition of LIMK2 did not affect the ROCK1 protein expression. The content of fibroblasts positive for phospho-LIMK2 in the H group returned to the level found in the S group, whereas it did not in the M group. However, the L group did not exhibit such improvements. Our data suggest that the inhibition of LIMK2, particularly with administration of 10.0 mg kg-1 body weight LIMK2i, can improve corporal fibrosis and erectile function by normalizing the LIMK2/Cofilin pathway.
Animals
;
Cofilin 1/metabolism*
;
Electric Stimulation
;
Erectile Dysfunction/etiology*
;
Fibroblasts/pathology*
;
Fibrosis/drug therapy*
;
Lim Kinases/antagonists & inhibitors*
;
Male
;
Penile Diseases/drug therapy*
;
Penis/innervation*
;
Peripheral Nerve Injuries/pathology*
;
Phosphorylation
;
Rats
;
Rats, Sprague-Dawley
;
Signal Transduction/drug effects*
;
rho-Associated Kinases/genetics*
6.Bilateral Macular Lesions Following Electrical Injury.
Chan WU ; Rong-Ping DAI ; Fang-Tian DONG ; Hong DU ; Hua ZHANG
Chinese Medical Sciences Journal 2016;31(3):196-199
7.Changes of CK-MB and HSP 60 in electrical-injuried rats.
Hui-tong LIU ; Gao-wen FU ; Ze ZHAO ; Su-zhen DING ; Qiao-feng WANG ; Lei CHEN ; Ya-nan XIE ; Zhen-yuan WANG
Journal of Forensic Medicine 2012;28(5):333-336
OBJECTIVE:
To investigate the changes of creatine kinase-MB (CK-MB) and heat shock protein 60 (HSP 60) in rats without electric marks after electric injury, to identify the relationship of the CK-MB, HSP 60 and the time of electric injuries, and to evaluate the damage to cells after electric injury.
METHODS:
The animal model of electric injury without electric marks was established by alternating current (voltage 110 V). Automatic biochemistry analyzer was used to detect the serum CK-MB and immunohistochemical staining technology was used to analyze the tissues of myocardium and left lobe of liver.
RESULTS:
The amount of serum CK-MB was increased when the rats were injuried, and reached the peak at 30min. Then the amount of CK-MB began to decrease and showed a slight downward trend in 3-5 h after electric injury, and leveled off at 6 h. Immunohistochemistry staining also showed the changes of HSP 60 of rats' myocardial cells and hepatic cells regularly after electric injury.
CONCLUSION
The regular changes of serum CK-MB and tissular HSP 60 in rats can be used to diagnosis electric injury and assess the injury of internal organs after the electric injury without electric marks.
Animals
;
Chaperonin 60/metabolism*
;
Creatine Kinase, MB Form/metabolism*
;
Electric Injuries/complications*
;
Immunohistochemistry
;
Liver/pathology*
;
Myocardium/pathology*
;
Rats
8.Study on electrical current mark with environmental scanning electron microscopy and energy dispersive X-ray microanalyser.
Dan LIU ; Hao WANG ; Shang-xun LI ; Xiang-tao MA ; Yi-jie DUAN ; Hong-yan ZHOU ; Yi-wu ZHOU
Journal of Forensic Medicine 2010;26(6):421-424
OBJECTIVE:
To provide objective proof on diagnosis of electrical current mark in electrocution, the environmental scanning electron microscopy and energy dispersive X-ray microanalyser (ESEM-EDX) were adopted to study the microscopic morphological characteristics and elemental composition of electrical current mark.
METHODS:
Morphological characteristics of electrical current marks, the elemental composition and morphology of metal particles were studied with ESEM-EDX.
RESULTS:
The electroporation and metal melted beads could be found in the electrical current marks and skin around them. The metal melted beads mainly composed of common metal such as iron, copper, aluminum and some uncommon metal including gold, titanium and barium.
CONCLUSION
ESEM-EDX can be applied in forensic diagnosis of electrocution.
Autopsy
;
Electric Injuries/pathology*
;
Electron Probe Microanalysis/methods*
;
Forensic Medicine/methods*
;
Humans
;
Metals, Heavy/analysis*
;
Microscopy, Electron, Scanning/methods*
;
Skin/pathology*
;
Trace Elements/analysis*
;
X-Rays
9.Pathology of accidental electrocution: an autopsy study of 16 cases.
Bo-Tao LUO ; Ying-Hai ZHAO ; Xiao-Yi CHEN ; Han-Guo JIANG
Chinese Journal of Pathology 2009;38(6):380-383
OBJECTIVETo study the pathologic findings seen in lethal cases due to accidental electrocution.
METHODSThe macroscopic and microscopic findings in 16 autopsy cases died of electrocution encountered during the period from January, 2001 to July, 2008 were retrospectively reviewed.
RESULTSTypical electric marks were found on gross examination in 5 of the 16 cases studied. Histologically, 11 of the 16 cases showed evidence of electric burn. The morphologic features of atypical electric marks varied. Simple epidermal exfoliation and color changes were relatively common. Pathologic changes in internal viscera included disarray of myocardial fibers. Rupture of myocardial fibers was readily identified than in non-electrocution death. Sometimes, focal interstitial hemorrhage and polarization of endothelial cells were seen.
CONCLUSIONSThe electric marks on the skin, as confirmed by histologic examination, remain important sequelae of electrocution. The pathologic changes seen in myocardium provide additional clues to the diagnosis.
Adolescent ; Adult ; Autopsy ; Burns, Electric ; pathology ; Child ; Child, Preschool ; Electric Injuries ; pathology ; Female ; Humans ; Male ; Middle Aged ; Myocardium ; pathology ; Retrospective Studies ; Skin ; pathology ; Young Adult
10.The effect of platelet-rich plasma on cavernous nerve regeneration in a rat model.
Xie-Gang DING ; Shi-Wen LI ; Xin-Min ZHENG ; Li-Quan HU ; Wan-Li HU ; Yi LUO
Asian Journal of Andrology 2009;11(2):215-221
The aim of this study was to investigate the effect of platelet-rich plasma (PRP) on cavernous nerve (CN) regeneration and functional status in a nerve-crush rat model. Twenty-four Sprague-Dawley male rats were randomly divided into three equal groups: eight had a sham operation, eight underwent bilateral nerve crushing with no further intervention and eight underwent bilateral nerve crushing with an immediate application of PRP on the site of injury. Erectile function was assessed by CN electrostimulation at 3 months and nerve regeneration was assessed by toluidine blue staining of CN and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining of penile tissue. Three months after surgery, in the group that underwent bilateral nerve crushing with no further intervention, the functional evaluation showed a lower mean maximal intracavernous pressure (ICP) and maximal ICP per mean arterial pressure (MAP) with CN stimulation than those in the sham group. In the group with an immediate application of PRP, the mean maximal ICP and maximal ICP/MAP were significantly higher than those in the injured control group. Histologically, the group with the application of PRP had more myelinated axons of CNs and more NADPH-diaphorase-positive nerve fibres than the injured control group but fewer than the sham group. These results show that the application of PRP to the site of CN-crush injury facilitates nerve regeneration and recovery of erectile function. Our research indicates that clinical application of PRP has potential repairing effect on CN and peripheral nerves.
Animals
;
Disease Models, Animal
;
Electric Stimulation
;
Erectile Dysfunction
;
pathology
;
physiopathology
;
therapy
;
Male
;
NADPH Dehydrogenase
;
metabolism
;
Nerve Regeneration
;
physiology
;
Penile Erection
;
physiology
;
Penis
;
innervation
;
Peripheral Nerve Injuries
;
Peripheral Nerves
;
metabolism
;
pathology
;
Platelet Transfusion
;
Platelet-Rich Plasma
;
Radiculopathy
;
etiology
;
pathology
;
physiopathology
;
Rats
;
Rats, Sprague-Dawley

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