Yong Gou Park

Injury in the spinal cord may produce cell death in the brain

Functional deficits after spinal cord injury have originated not only from the direct physical damage itself, but from the secondary biochemical and pathological changes. Apoptotic cell death has been seen around the periphery of an injured site and has been known to ultimately progress to necrosis and infarction. We have initiated the present study focusing on the role of apoptosis in the secondary injury of the brain after acute spinal cord injury (SCI), and conducted a series of experiments, the study examining the morphological changes in the brain following the spinal injury. Under pentobarbital anesthesia, male Sprague-Dawley rats were subjected to SCI model. Rats were laminectomized and SCI was induced using NYU spinal impactor at T9 segment. The behavioral test was performed. Electrophysiologically, motor evoked potentials (MEPs) were recorded. The animals were subjected to morphological study at 12, 24, 48, 72 h, and 1 week, postoperatively. Locomotor deficits were observed after SCI, and changes in the amplitudes and latencies of the MEPs were observed. The morphological changes were evidenced by terminal TUNEL staining and Calbindin-D(28K) immunohistochemistry. The TUNEL-positive cells were located at the brain motor cortex after SCI. TUNEL-positive cells were seldom found 4 h after injury. In addition, Calbindin-D28K immunoreactive neurons were observed in the motor cortex after injury. These results suggest that apoptosis may play an important role in the pathophysiology of the brain motor cortex following acute spinal cord injury and functions that were deteriorated after SCI may be related to these electrophysiological and morphological changes.

Percutaneous Radiofrequency Lumbar Facet Rhizotomy in Mechanical Low Back Pain Syndrome

During the period from March 1992 to June 1996, we performed percutaneous radiofrequency (RF) facet rhizotomy in 324 patients with low back pain. Employing the lesion generator, we coagulated branches of the zygapophyseal nerve to treat low back pain. The follow-up period was 6-51 months (average: 22.5 months). There were no complications during the procedure and the follow-up period and no poor results were observed. Two-hundred and thirty-one patients (103 females and 128 males) had mechanical low back pain syndrome and showed marked improvement of pain after the procedure, including 29 cases with previous spinal surgery. We concluded that percutaneous RF facet rhizotomy is a safe and effective procedure for low back pain patients, especially for those with mechanical low back pain syndrome.

MICROVASCULAR DECOMPRESSION AND PERCUTANEOUS RHIZOTOMY IN TRIGEMINAL NEURALGIA

We analyzed 417 patients with trigeminal neuralgia who underwent microvascular decompression (MVD; n = 146) or percutaneous procedures, i.e. radiofrequency rhizotomy (RFR; n = 235) and glycerol rhizotomy (GR; n = 36) between March 1973 and December 1996. MVD and RFR showed the highest rates of initial pain relief (MVD 96.5%; RFR 92.3%; GR 82.8%). RFR and GR had 5.1 and 3.3% rates of facial dysesthesia, respectively, and MVD had the lowest rate (0.3%). Among 9 cases (8.6%) with recurrences after MVD, 8 cases underwent RFR and all of them obtained good long-term results (7.2 years on average). We concluded that MVD is the treatment of choice for tolerant younger patients and should be recommended for patients who desire no sensory deficit. We also determined that radiofrequency rhizotomy is the procedure of choice for patients in whom MVD failed.

Dehydroascorbic acid prevents oxidative cell death through a glutathione pathway in primary astrocytes

Ascorbic acid (AA) is a well‐known antioxidant. It also has pro‐oxidant effects, however, in the presence of free transition metals. Because of the pro‐oxidant effects of AA, dehydroascorbic acid (DHA), an oxidized form of AA, has been used as a substitute for AA. DHA has been shown recently to have a protective effect in an experimental stroke model. This study was carried out to determine if DHA has different effects from AA on hydrogen peroxide (H2O2)‐induced oxidative cell death in primary astrocytes. DHA was found to prevent cell death and reverse mitochondrial dysfunction after exposure to H2O2. DHA significantly increased the glutathione peroxidase (GPx) and glutathione reductase (GR) activities 1 hr after H2O2 exposure. Moreover, DHA not only reversed the decrease in the glutathione (GSH) levels, but also significantly enhanced it by stimulating the pentose phosphate pathway (PPP) 15 hr after H2O2 exposure. DHA also reduced production of reactive oxygen species (ROS) after H2O2 exposure. In contrast, AA accelerated H2O2‐induced cell death. To determine if the pro‐oxidant effect of AA is related to iron, the effect of AA on cell death was examined using an iron chelator, desferrioxamine. Even though co‐pretreatment with AA and desferrioxamine could abrogate the aggravating effects of AA on H2O2‐induced cell death at early stages, it could not prevent H2O2‐induced cell death over a 24‐hr period. These results suggest that DHA has distinct effects from AA and prevent H2O2‐induced cell death by increasing the GSH levels mediated by the GPx and GR activities and PPP.

Microinjection of opiates into the periaqueductal gray matter attenuates neuropathic pain symptoms in rats.

&NA; We have previously demonstrated that electrical stimulation of the ventral periaqueductal gray matter (PAG) produced analgesia in neuropathic pain in rats. Opioids were also shown to be involved in analgesic effects. This study sought to determine whether opiates microinjected into the ventral PAG produce analgesia. Male Sprague–Dawley rats were chronically implanted with a guide cannula in the PAG under pentobarbital anesthesia and both the tibial and sural nerves were completely cut. Pain sensitivity was postoperatively measured with a von Frey filament and acetone applied to the sensitive area for 1 week. Opioids such as [D‐Ala2,N‐MePhe4,Gly(ol)5]‐enkephalin (DAMGO) and [D‐Pen2,D‐Pen5]‐enkephalin (DPDPE) were injected into the PAG. DAMGO, a γ‐opioid agonist, and DPDPE, a δ‐opioid agonist, were highly effective in reducing neuropathic pain. These effects were reversed by naloxone. These results suggest that the neurons in the ventral PAG are activated by opioids to produce analgesia and that specific opioid receptors are involved in the descending pain inhibition system from the PAG.

Antiallodynic effects produced by stimulation of the periaqueductal gray matter in a rat model of neuropathic pain

It has been well documented that there is opioid resistance in neuropathic pain. This indicates that the endogenous opioid system may not be involved effectively in modulating neuropathic pain. The present study sought to determine if activation of the descending pain inhibition system might produce analgesia in the animal neuropathic model we developed. Under ketamine anesthesia, male Sprague-Dawley rats were chronically implanted with stimulating electrodes in the ventral periaqueductal gray matter (PAG) and both the tibial and sural nerves of the sciatic nerve branches were severed. Pain sensitivity was measured with a von Frey filament and acetone applied to the sensitive area for 1 week postoperatively. Rats with neuropathic pain syndrome after transection of the tibial and sural nerves were tested as to the analgesic effects of ventral PAG stimulation for an additional two weeks. Electrical stimulation of the ventral PAG turned out to be highly effective in alleviating neuropathic pain. Mechanical allodynia and cold allodynia were reduced by PAG stimulation. Naloxone reversed the antiallodynic effects of ventral PAG stimulation. These results suggest that activation of the descending pain inhibition system including the ventral PAG reduces neuropathic pain syndrome and that opiates are involved in this system.

Effects of methylprednisolone on the neural conduction of the motor evoked potentials in spinal cord injured rats.

Methylprednisolone (MP), a glucocorticoid steroid, has an anti-inflammatory action and seems to inhibit the formation of oxygen free radicals produced during lipid peroxidation in a spinal cord injury (SCI). However, the effects of MP on the functional recovery after a SCI is controversial. The present study was conducted to determine the effects of MP on the recovery of neural conduction following a SCI. A SCI was produced using the NYU spinal cord impactor. A behavioral test was conducted to measure neurological disorders, and motor evoked potentials (MEPs) were recorded. According to the behavioral test, using BBB locomotor scaling, MP-treated animals showed improved functional recoveries when compared to salinetreated animals. MEP latencies in the MP-treated group were shortened when compared to those in the control group. Peak amplitudes of MEPs were larger in the MP-treated group than those in the control group. The thresholds of MEPs tended to be lower in the MP-treated group than those in the control group. These results suggest that MP may improve functional recovery after a SCI.

Complications Following Gamma Knife Radiosurgery

Between May 1992 and February 1994, 213 lesions in 183 consecutive patients were treated with Gamma Knife radiosurgery at Severance Hospital, Yonsei University, Seoul, Korea. During this period, we experienced 2 deaths, 1 directly and another indirectly related to irradiation. Nonfatal complications included 1 tumor bleeding, and 4 ventriculoperitoneal shunts had to be inserted due to aggravation of preexisting hydrocephalus. Radiation-induced imaging changes developed in 23.6% of the cases followed up for more than 6 months. Among 24 lesions of 8 cavernous hemangiomas, all 4 cases with lesions larger than 1.5 cm3 developed imaging changes.

Crossed-withdrawal reflex in a rat model of neuropathic pain: implications in neural plasticity

Recently we developed a neuropathic rat model employing a distal sciatic nerve branch injury, in which rats show vigorous behavioral signs of neuropathic pain. This study was performed to evaluate the crossed-withdrawal reflex in which any stimuli applied to the uninjured side produces allodynic signs on the injured side in our neuropathic pain model. Rats that received neuropathic surgery developed behavioral signs of neuropathic pain. In addition, these rats developed pain responses of the injured paw to stimuli applied to the contralateral uninjured paw, therefore, demonstrating the crossed-withdrawal reflex. Moreover, electrical stimulation of the uninjured paw developed evoked potentials in the ventral root on the injured side. These results suggest that information processing from input on the uninjured side to output on the injured side, can be facilitated in rats with a nerve injury and that neuroplasticity may contribute to the crossed-withdrawal reflex.

Selection of treatment modalities for cerebral arteriovenous malformations: a retrospective analysis of 348 consecutive cases

The objective was to establish the selection criteria for the optimal management modalities for cerebral arteriovenous malformations. We analysed the complications and late outcomes in 348 consecutive cases (132 microsurgical resections, 202 stereotactic radiosurgeries, 8 embolisations only, 6 combined treatments) managed at Yonsei University Hospital from 1988 to 1997. Files for all patients were analysed. The outcome was classified into good for the patients who returned to their previous job with or without neurological deficits, fair for the patients who were unable to return to work but performed daily activities independently with minor deficits, and poor for the patients who were performing dependent daily activities with major deficits. The outcome of microsurgery was considered good in 108 patients (81.8%), fair in 18 (13.6%), poor in 4 (3.1%), and 2 (1.5%) patients died. Initial insults and haemodynamic complications were the major cause of an unfavourable outcome. The cumulative occlusion rate of the nidus after radiosurgery was 10.2% within 12 months, 75.3% within 24 months, and 89.8% within 36 months. Perilesional imaging changes with neurological deficits (4 permanent and 6 transient, 4.8%) and haemorrhage (16 patients, 7.7%) during the latent interval were the major cause of an unfavourable outcome (1 poor, 4 dead after radiosurgery). Postradiosurgery bleeding occurred frequently within 6 months (6 patients), and between 13 and 24 months (8 patients). In conclusion, selection of treatment modality for cerebral AVMs depends on the preoperative evaluation of the risk/benefit ratio in each case. Microsurgical removal, which eliminates the risk of bleeding immediately, is preferred for lesions in non-eloquent areas. Radiosurgery is an effective treatment modality for small lesions in eloquent areas, but has a substantial risk of haemorrhage during the latency period. Results of this study suggest that microsurgical removal should be considered for lesions in eloquent areas with high haemorrhage risk, such as prior haemorrhage, medium to large size lesion, and single deep venous drainage.