Described here is a case of accidental intrathecal administration of vincristine with pathologic findings in the central nervous system. A 3-year-old boy with acute lymphoblastic leukemia, was given his ninth course chemotherapy. Vincristine was accidentally injected intrathecally. The clinical course was rapidly progressive (6-day course) and resulted in death. An autopsy was done. The brain and spinal cord was grossly edematous and congested without any specific feature. Histologically, profound loss of neuron was noted in the spinal cord. Remaining neurons in the spinal cord, particularly anterior horn cells were markedly swollen. The spinal nerves show diffuse axonal degeneration and myelin loss. The upstream portion of the spinal cord (brain stem, cerebellum, cerebrum) showed patchy loss of neurons, especially Purkinje cells and granular cells of the cerebellar cortex. Many neurons showed axonal reaction (chromatolysis) with swelling. Several neurons show intracytoplasmic eosinophilic inclusion body. Myelin loss, axonal swelling and enlargement of perivascular spaces were seen throughout the white matter of central nervous system.
Antineoplastic Agents/therapeutic use* ; Brain/pathology ; Brain/drug effects ; Case Report ; Central Nervous System/pathology ; Central Nervous System/drug effects* ; Child, Preschool ; Fatal Outcome ; Histocytochemistry ; Human ; Injections, Spinal ; Leukemia, Lymphocytic, Acute/drug therapy* ; Male ; Medication Errors* ; Spinal Cord/pathology ; Spinal Cord/drug effects ; Spinal Nerves/pathology ; Spinal Nerves/drug effects ; Vincristine/therapeutic use* ; Vincristine/administration & dosage

OBJECTIVETo study the effects of Ginkgo biloba extract (GBE) on lipid peroxidation and apoptosis after spinal cord ischemia/reperfusion (I/R) in rabbits.

METHODSSpinal cord I/R injury model was established according to the description of Erten et al. A total of 27 New Zealand white rabbits were divided into three groups randomly: a sham group (9 rabbits treated with sham operation but without aortic occlusion), a model group (9 rabbits treated with aortic occlusion and volume-matched saline), and a GBE group (9 rabbits treated with aortic occlusion and Ginaton (100 mg/kg) injected 30 minutes before aortic clamping and at the onset of reperfusion). The neurological outcomes were evaluated at 24 and 48 hours after reperfusion, respectively. The spinal cord malondialdehyde (MDA) level, superoxide dismutase (SOD) were then detected. Neural cell apoptosis was determined by terminal deoxynucleotidyl t-ransferase (TdT)-mediated dUTP-fluorescence nick end labeling (TUNEL) method and the expression of bcl-2 and bax were examined histologically in the spinal cord with immunohistochemistry.

RESULTSI/R produced a significant decrease in neurological scoring. The motor scores of the GBE group were significantly higher than those of the model group at 24 and 48 hours after reperfusion (P<0.05). Compared with the model group, GBE ameliorated the down-regulation of SOD and produced a significant reduction of the MDA level (P<0.01). The positive cells for TUNEL in the model group were much more than those of the GBE group (P<0.01). The bcl-2 was up-regulated after I/R, especially in the GBE group (P<0.01). The up-regulation of bax was greatly diminished by GBE (P<0.01).

CONCLUSIONSGBE has protective effects against spinal cord I/R injury, and the mechanism may be that it can scavenge oxygen free radicals and inhibit the apoptosis of neural cells.

Animals ; Apoptosis ; drug effects ; Ginkgo biloba ; Lipid Peroxidation ; drug effects ; Malondialdehyde ; analysis ; Neuroprotective Agents ; therapeutic use ; Phytotherapy ; Plant Extracts ; therapeutic use ; Rabbits ; Reperfusion ; Spinal Cord ; drug effects ; pathology ; Spinal Cord Ischemia ; metabolism ; pathology ; Superoxide Dismutase ; analysis

OBJECTIVETo investigate the dynamic changes of neurofilaments (NFs) proteins in spinal cords of hens with phenylmethylsulfonyl fluoride (PMSF) pretreatment for exploring the mechanism of tri-o-cresyl phosphate (TOCP)-induced delayed neuropathy (OPIDN).

METHODAdult Roman hens were randomly divided into three groups, control, TOCP and PMSF + TOCP. Birds in PMSF + TOCP set were pretreated with PMSF, 24 hours later, hens in both TOCP group and PMSF + TOCP group were administrated with TOCP at a single dosage of 750 mg/kg. Then all animals were sacrificed on the corresponding time-points of 1, 5, 10, and 21 days respectively after dosing of 750 mg/kg TOCP. The spinal cords were dissected, homogenized, and centrifuged at 100,000 x g. The levels of high molecular neurofilament (NF-H), medium molecular neurofilament (NF-M) and low molecular neurofilament (NF-L) in both pellet and supernatant fractions of spinal cords were determined by SDS-PAGE and Western-blotting.

RESULTSThe hens in TOCP group showed paralysis gait at the end of 21-day experimental period. The levels of NFs proteins in spinal cords changed obviously. Compared with control, the NFs in pellet showed a dramatic decrease on day 10 and then followed by a recovery. In the supernatant, the NFs proteins showed similar changes, which decreased significantly on day 10 and almost recovered control on day 21. Such as, NF-L, NF-M and NF-H decreased by 51%, 86% and 38% on day 10. The OPIDN signs were not observed in PMSF + TOCP group, and imbalances of NFs were obviously alleviated. Compared with control, only NF-M in pellet increased by 21% (P < 0.05) on day 21, others remained no changes; The levels of NF-H and NF-M in supernatant respectively increased by 19% and 35% on day 21, others were no significant statistical differences.

CONCLUSIONTOCP may induce imbalance of NFs levels in progress of OPIDN, and PMSF pretreatment may protect animals from OPIDN by reducing above changes, which may explain that TOCP-induced imbalance of NFs may be connected with the occurrence and development of OPIDN.

Animals ; Chickens ; Female ; Neurofilament Proteins ; drug effects ; Phenylmethylsulfonyl Fluoride ; pharmacology ; Protein Subunits ; drug effects ; Spinal Cord ; drug effects ; metabolism ; pathology ; Tritolyl Phosphates ; toxicity

OBJECTIVETo study the toxicological effects of benzo[a]pyrene(BaP) on mammalian animal's nerve tissue.

METHODS50 Kunming mice were divided into 5 groups at random, the exposed groups(3 dose level groups), the vehicle control group and standard control group. Every group got 10 mice. The exposed groups were treated by intraperitoneal injection with BaP dissolved in vegetable oil at 7.8, 3.2 and 1.3 mg/kg respectively, 4 times/week, for 10 weeks, the vehicle control group were given vegetable oil and the standard control group were not given any treatment. All the mice were anesthetized with 0.02 mol/L pentobarbital and infused with 1.33 mol/L paraformaldehyde dissolved in PBS through heart after 10 weeks. Then the brain, spinal cord and sciatic nerve were removed. Slices of these tissues were made and morphological changes were observed by optical microscope and electron-microscope. Cell appoptosis was examined by TUNEL(TdT-mediated x-dUTP nick end labeling) method.

RESULTSMorphological observations showed tissue injury in BaP exposed groups. There were focal necrosis areas found in the high-dose group. The cell apoptosis rates in 3.2 and 1.3 mg/kg groups were 90.02%-94.22% and 62.45%-77.54% respectively, significantly higher than those of vehicle control group and standard control group(4.60%-5.57%).

CONCLUSIONBaP is neurotoxic. It could damage the nerve tissue as well as induce DNA breaks and cell apoptosis.

Animals ; Apoptosis ; drug effects ; Benzo(a)pyrene ; toxicity ; Brain ; drug effects ; pathology ; Dose-Response Relationship, Drug ; In Situ Nick-End Labeling ; Mice ; Sciatic Nerve ; drug effects ; pathology ; Spinal Cord ; drug effects ; pathology

OBJECTIVETo explore the possibility of peripheral nerve damage induced by antiepileptic drugs (AEDs) in different age rats and its pathogenesis.

METHODSAdult (2-month-old) and infant (7-day-old) rats were divided into 8 groups (n = 16 in each) and treated with the following 7 AEDs respectively: phenytoin [PHT, 62.5 mg/(kgxd)], phenobarbital [PB, 30.0 mg/(kgxd)], sodium valproate [VPA, 312.5 mg/(kgxd)], clonazepam [CZP, 1.25 mg /(kgxd)], carbamazepine [CBZ, 187.5 mg/(kgxd)], topiramate [TPM, 40 mg/(kgxd)], oxcarbazepine [OXC, 312.5 mg/(kgxd)], remaining one group was used as control. Four weeks later, 8 rats were sacrificed randomly from each group and serum, sciatic nerves and spinal cord samples were collected. The rest half rats were sacrificed 4 week after AEDs withdrawal. Histological observations were performed on the sciatic nerves samples, including teased fibers, semi-thin sections and electron microscopy. The activity of total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in serum and sciatic nerves were detected respectively. Expression of apoptosis-related proteins Bcl-2 and Bax was detected by immunohistochemistry. Neurons apoptosis in the anterior horns of spinal cord were detected by TUNEL.

RESULTS(1) Except for TPM group, various incidence (7.2% - 20.2%) of teased fibers abnormalities were observed in all the other different age groups. PHT group showed the most serious changes followed by PB (adult) or VPA (infant), CBZ, CZP and OXC groups. The predominant abnormality of teased fibers was demyelination. (2) There was no significant difference in the incidence of pathologic changes in teased fibers between adult and infant groups. Four weeks after AEDs withdrawal, recovery of pathologic changes in teased fibers in infant groups was much better than adult. (3) Significantly increased expression of Bax protein and ratio of Bax/Bcl-2 was only found in infant rats treated with PB, CNP or VPA compared with control (P < 0.05), the results of TUNEL was in accordance with immunohistochemistry. (4) Compared with control, the activity of T-AOC and SOD decreased in both infant and adult rats treated with PHT, CZP, CBZ and OXC, and the reduction of SOD activity in serum and sciatic nerves samples was also found in PB groups. Serum activity of GSH-PX was decreased in both age groups treated with PHT, PB, VPA, CZP, CBZ and OXC. The reduction of GSH-PX activity in sciatic nerves samples was remarkably in both adult and infant rats treated with PHT, PB, CBZ, OXC as well as the infant rats treated with CZP.

CONCLUSIONSSix AEDs (PHT, PB, CBZ, VPA, CZP, OXC) showed the potential to cause peripheral nerves damage. Demyelination was the predominant pathologic change. Both adult and infant rats had the same susceptibility. Recovery of pathologic changes in teased fibers in both age groups was slow, but infant rats were prone to revive more quickly. There was no significant correlation between spinal cord neuron apoptosis and peripheral nerves damages in rats treated with AEDs. Breakdown of oxidation-antioxidation balance was closely related to development of peripheral nerves damages caused by most AEDs.

Animals ; Anticonvulsants ; adverse effects ; Demyelinating Diseases ; chemically induced ; pathology ; Oxidative Stress ; Peripheral Nerves ; drug effects ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve ; pathology ; Spinal Cord ; pathology

The aim of this study is to investigate the effects of electroacupuncture, corticosteroid, and combination of two treatments on ambulatory paresis due to spinal cord injury in dogs by comparing therapeutic effects of electroacupuncture and corticosteroid. Spinal cord injury was induced in twenty healthy dogs (2.5~7 kg and 2~4 years) by foreign body insertion which compressed about 25% of spinal cord. There was no conscious proprioception, no extensor postural thrust, and ambulatory. Dogs were divided into four groups according to the treatment; corticosteroid (group A), electroacupuncture (group B), corticosteroid and electroacupuncture (group AB), and control (group C). Neurological examination was performed everyday to evaluate the spinal cord dysfunction until motor functions were returned to normal. Somatosensory evoked potentials (SEPs) were measured for objective and accurate evaluations. The latency in measured potentials was converted into the velocity for the evaluation of spinal cord dysfunctions. Pain perceptions were normal from pre-operation to 5 weeks after operation. Recovery days of conscious proprioception in groups A, B, AB, and C were 21.2+/-8.5 days, 19.8+/-4.3 days, 8.2+/-2.6 days, and 46.6+/-3.7 days, respectively. Recovery days of extensor postural thrust in group A, group B, group AB, and group C were 12.8+/-6.8 days, 13.8+/-4.8 days, 5.4+/-1.8 days, and 38.2+/-4.2 days, respectively. There were no significant differences between group A and group B. However, recovery days of group AB was significantly shorter than that of other groups and that of group C was significantly delayed (p<0.05). Conduction velocities of each group were significantly decreased after induction of spinal cord injury on SEPs (p<0.05) and they showed a tendency to return to normal when motor functions were recovered. According to these results, it was considered that the combination of corticosteroid and electroacupuncture was the most therapeutically effective for ambulatory paresis due to spinal cord injury in dogs.
Animals ; Anti-Inflammatory Agents/*therapeutic use ; Dogs ; Electroacupuncture/*veterinary ; Evoked Potentials, Somatosensory/drug effects ; Female ; Male ; Methylprednisolone Hemisuccinate/pharmacology/*therapeutic use ; Spinal Cord/drug effects/pathology ; Spinal Cord Compression/drug therapy/*therapy/*veterinary

Aconite is a common remedy of herb doctors and is widely used in the Far East. Clinical aspects of the visual disturbance produced by this drug have been described, but little is known about its pathology. Tinctura aconiti (0.6 mg of total alkaloid/kg 2x) was administered intraperitoneally in rabbits to evaluate its toxic effects on the visual system. The alteration in the visual evoked potential following aconite injection consisted of a delay in the onset and peak latency. Histopathologically, there were damages to the myelin sheath of the visual pathway, spinal cord and peripheral nerves. These findings suggest that aconite may cause primarily myelo-optic neuropathy.
Aconitum/administration & dosage/*toxicity ; Animals ; Evoked Potentials, Visual/*drug effects ; Injections, Intraperitoneal ; Myelin Sheath/*drug effects/ultrastructure ; Optic Nerve/*drug effects/ultrastructure ; Optic Nerve Diseases/*chemically induced/pathology ; Rabbits ; Spinal Cord/*drug effects/ultrastructure

Peripheral itch stimuli are transmitted by sensory neurons to the spinal cord dorsal horn, which then transmits the information to the brain. The molecular and cellular mechanisms within the dorsal horn for itch transmission have only been investigated and identified during the past ten years. This review covers the progress that has been made in identifying the peptide families in sensory neurons and the receptor families in dorsal horn neurons as putative itch transmitters, with a focus on gastrin-releasing peptide (GRP)-GRP receptor signaling. Also discussed are the signaling mechanisms, including opioids, by which various types of itch are transmitted and modulated, as well as the many conflicting results arising from recent studies.
Action Potentials ; drug effects ; Analgesics, Opioid ; pharmacology ; Animals ; Humans ; Pruritus ; metabolism ; pathology ; Sensory Receptor Cells ; metabolism ; Spinal Cord ; pathology ; Synaptic Transmission ; physiology

BACKGROUNDThe iron catalyzed lipid peroxidation plays an important role in the autodestruction of the injured spinal cord. This study was to detect the antioxidation of melatonin against spinal cord injury (SCI) in rats.

METHODSSity Sprague-Dawley rats were randomly divided into four groups: group A (n = 15) for laminectomyanly, group B (n = 15) for laminectomy with SCI, group C (n = 15) for SCI and intraperitoneal injection of a bolus of 100 mg/kg melatonin, and group D (n = 15) for SCI and intraperitoneal injection of saline containing 5% ethanol. The SCI of animal model was made using modified Allen's method on T12. Six rats of each group were sacrificed 4 hours after injury, and the levels of free iron and malondialdehyde (MDA) of the involved spinal cord segments were measured by the bleomycin assay and thiobarbituric acid (TBA) separately. Functional recovery of the spinal cord was assessed by Modified Tarlov's scale and the inclined plane method at 1, 3, 7, 14, 21 days after SCI. The histologic changes of the damaged spinal cord were also examined at 7 days after SCI.

RESULTSAfter SCI, the levels of free iron and MDA were increased significantly and the modified Tarlov's score and inclined plane angle decreased significantly in groups B and D. In group C, the Tarlov's score and inclined plane angle were increased significantly at 7, 14 and 21 days, with histological improvement.

CONCLUSIONMelatonin can reduce the level of lipid peroxidation and prevent damage to the spinal cord of rat.

Animals ; Antioxidants ; therapeutic use ; Iron ; analysis ; Lipid Peroxidation ; drug effects ; Male ; Malondialdehyde ; analysis ; Melatonin ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Injuries ; drug therapy ; metabolism ; pathology

Evidence suggested that glycogen synthase kinase-3β (GSK-3β) is involved in Nogo-66 inhibiting axonal regeneration in vitro, but its effect in vivo was poorly understood. We showed that stereotactic injection of shRNA GSK-3β-adeno associated virus (GSK-3β-AAV) diminished syringomyelia and promoted axonal regeneration after spinal cord injury (SCI), using stereotactic injection of shRNA GSK-3β-AAV (tested with Western blotting and RT-PCR) into the sensorimotor cortex of rats with SCI and by the detection of biotin dextran amine (BDA)-labeled axonal regeneration. We also determined the right position to inject into the sensorimotor cortex. Our findings consolidate the hypothesis that downregulation of GSK-3β promotes axonal regeneration after SCI.
Animals ; Axons ; drug effects ; metabolism ; Dependovirus ; genetics ; Glycogen Synthase Kinase 3 beta ; genetics ; metabolism ; Humans ; Nerve Regeneration ; genetics ; RNA, Small Interfering ; administration & dosage ; genetics ; Rats ; Sensorimotor Cortex ; drug effects ; pathology ; Spinal Cord Injuries ; genetics ; pathology ; therapy ; Syringomyelia ; genetics ; pathology ; therapy