Systemic effects of isolated brain injury: an experimental animal study.

OBJECTIVE: Although various experimental works of neurotrauma research are performed, little attention has been paid to the concomitant systemic changes following isolated traumatic brain injury (TBI). Such investigations seem to be a prerequisite condition for evaluation of experimental drugs, which may diminish the secondary damage following TBI. We describe histopathologic findings of the lung, liver, spleen and kidney 96 hours following an experimental TBI. METHODS: Ten male C57BI/6 mice were subjected to a controlled cortical impact (CCI) over the left parietotemporal cortex using rounded-tip impounder for application of a standardized brain injury. Subjects were killed 96 hours following trauma. Brain, lung, liver, kidney and spleen were preserved for morphologic examinations. RESULTS: Moderate histopathologic changes were evident in the lung and liver. The kidney and spleen seem not to be affected by the trauma regarding our examination. CONCLUSION: The findings of this study show that even isolated TBI can lead to a migration of immunocompetent cells to peripheral organs potentially leading to dysfunctions of peripheral organs to various extents. More attention to peripheral organs during experimental TBI research is indicated.

Management of skull based meningiomas in the elderly patient.

BACKGROUND: The demographic evolution of Western society together with availability of modern imaging techniques leads to an increasing diagnosis of meningioma patients over 70 years of age. This raises the question of appropriate management of this histologically benign tumour in a geriatric population. DESIGN: Forty-three patients aged over 70 years were analyzed and matched in a retrospective study with a younger group of 89 patients according to tumour size, histology, symptoms, recurrence and presence of neurofibromatosis II. RESULTS: Changes in postoperative Karnofsky scores were not statistically different between the two age groups. Neurological outcome was worse among the younger group (12% vs. 7% deterioration). Regarding surgical complications we noted only a statistically significant higher infection rate in the geriatric age group. There was no peri-operative mortality. CONCLUSIONS: Age alone is not a criterion to deny a priori skull base surgery, since well selected geriatric patients may benefit from a meningioma operation that may enhance future quality of life.

Interdisciplinary reconstruction of oncological resections at the skull base, scalp and facial region.

Extensive bone and soft tissue defects of the skull require unique plastic and reconstructive techniques to avoid and optimize aesthetic appearance following oncological resections. Procedures are ideally planned in an interdisciplinary board composed of neurosurgery, otorhinolaryngology, plastic and reconstructive surgery to facilitate reconstructive procedures of soft tissue and bone as early as possible in one approach. Large resections may require plastic surgery involvement from the beginning. Herein, we describe the function of a multidisciplinary approach to complex oncologic resections of the cranial base, scalp, and facial regions for neuro-oncologic patients.

Trigeminocardiac reflex during skull base surgery: mechanism and management.

BACKGROUND: We study the occurrence and management of the trigeminocardiac reflex (TCR) during neurosurgical procedures for lesions of the skull base. METHOD: Two hundred patients underwent neurosurgical procedures for various skull base lesions and were evaluated retrospectively for the occurrence of the TCR during surgery. This phenomenon was defined as the onset of bradycardia lower than 60 beats/minute and hypotension with a drop in mean arterial blood pressure of 20% or more due to intra-operative manipulation or traction on the trigeminal nerve. FINDINGS: Sixteen patients (8%) had a TCR intra-operatively (7 vestibular schwannomas, 5 sphenoid wing meningiomas, 3 petroclival meningiomas, 1 intracavernous epidermoid cyst). In all 16 patients with a TCR the postoperative courses presented no complications that could be directly related to this intra-operative phenomenon. CONCLUSIONS: Due to the intracranial course of the trigeminal nerve several surgical procedures at the anterior, middle and posterior skull base may elicit the trigeminocardiac reflex. Continuous monitoring of hemodynamic parameters allows the surgeon to interrupt surgical manoeuvres immediately upon the occurrence of the TCR. This technique is sufficient for the heart rate and the arterial blood pressure to return to normal levels without the necessity of additional anticholinergic medication.

Alteration of rCBF in skull base lesions.

Cerebral functional imaging methods provide complementary information on brain function and large vessels regulatory controls which are compromised in cranial base lesions. The presence of a skull base tumor can alter regional cerebral blood flow (rCBF) in adjacent and remote brain tissue. This report presents the results of 104 CBF studies in 66 patients with skull base lesions (aged 17-75 years). The lesions included 36 meningiomas, 21 neurinomas and 9 other tumors. Regional CBF in tumor and brain tissue was measured prior to treatment using stable xenon enhanced computed tomography (Xenon(/T). For the quantitative analysis, regions of interest were delineated on tumor regions, cerebral and cerebellar hemispheres including peritumoral regions. In order to assess the remote effect of cerebellopontine angle (CPA) tumors, the brainstem, cerebellar, and cerebral blood flow were measured in 26 cases. The average brainstem CBF for patients with good outcome was higher than the average brainstem CBF for patients with poor outcome. This indicates that CBF studies in posterior fossa can be useful in predicting the prognosis of CPA tumor patients. We report a series of 16 patients with cavernous sinus tumors in whom the internal carotid artery was affected by the tumor. In nearly all cases Xenon/CT CBF studies with acetazolamide test showed no significant difference in hemispheric perfusion and a sufficient cerebrovascular reserve capacity. Interhemispheric asymmetry was present only in one patient. These results possibly indicate that i.v. administration of acetazolamide might contribute in selecting patients with higher risk for ischemic deficits after cavernous sinus surgery. Skull base meningiomas showed very high blood flow with a wide range. Local CBF in the peripheral region of meningiomas was higher than in the central region. Blood flow values in the peritumoral areas are about 30% lower than those of the ipsilateral hemisphere. In individual cases, blood flow values in the peritumoral low-density area on CT were extremely low. It is concluded that CBF studies in skull base tumors are valuable in treatment planning. Xenon/CT can be useful additional diagnostic procedure in the evaluation of skull base surgery candidates.

Xenon/CT CBF measurements as valuable diagnostic tool in a case of bilateral occlusive cerebrovascular disease associated with intracranial aneurysm.

A patient with the coincidental occurrence of a right internal carotid artery (ICA) stenosis and asymptomatic ipsilateral infraclinoidal ICA aneurysm is presented. CBF measurements including testing of the cerebrovascular reserve capacity (CRC) demonstrated a compromise of cerebral blood flow (CBF) within the anterior circulation of the affected side. We treated the patient in one operation by aneurysm clipping and subsequent carotid endarterectomy (CEA). 10 months later she presented with an occlusion of the contralateral ICA. CBF measurements showed sufficient resting flow and CRC on both sides. One year later repeat measurements disclosed a lowered resting CBF and diminished CRC on the affected side. Extracranial/Intracranial (EC/IC) artery bypass improved both symptoms and CBF/CRC values. The authors propose to treat symptomatic ICA stenosis and concurrent silent ipsilateral intracranial aneurysms at once if the patient is eligible for aneurysm surgery. CBF measurements should be performed before surgery. In a medically compromised patient carotid endarterectomy alone appears to be justifiable. In cases of symptomatic aneurysm and concurrent ICA stenosis a CEA can be added to aneurysm clipping to improve the hemodynamic situation for a better postoperative management. Xenon/CT investigations are suitable to provide important cerebral blood flow information. Together with angiography and clinical judgment it allows to identify patients with hemodynamic insufficiency. These are suitable candidates for an operative procedure to augment cerebral blood flow and to improve symptoms.

Comparison of unilateral and bilateral intrastriatal 6-hydroxydopamine-induced axon terminal lesions: evidence for interhemispheric functional coupling of the two nigrostriatal pathways.

Partial lesions of the nigrostriatal dopamine system can be induced reliably by the intrastriatal injection of 6-hydroxydopamine (6-OHDA) and are considered to be analogous to the early stages of human Parkinson's disease. Previous studies have established a clear correlation between different doses and placements of the 6-OHDA toxin and the degree of neurodegenerative changes and behavioral impairments. In the present study, the influence of the interdependence between the two nigrostriatal systems in both hemispheres on the effects on sensorimotor behavioral performances after terminal 6-OHDA lesions was investigated. The behavioral effects were correlated to the extent of nigral dopamine neuron cell and striatal tyrosine-hydroxylase (TH)-positive fiber loss. Sprague-Dawley rats receiving unilateral intrastriatal 6-OHDA injections (4 x 5 microg) exhibited a 30-70% reduction in striatal TH-positive fiber density along an anterior-posterior gradient, an 80% loss of nigral dopamine neurons and a mild degree of behavioral impairments as revealed by amphetamine-induced rotational asymmetry, and a reduced performance in the stepping and postural balance tests. When the same amount of toxin was injected twice into both hemispheres (2 x 4 x 5 microg), additional behavioral deficits were observed, consisting of a significant, but temporary, weight loss, a stable reduction in general locomotor activity and explorational behavior, and a long-term deficit in skilled forelimb use. This is interesting in light of the morphological findings, in which uni- and bilaterally lesioned animals did not differ significantly in the extent of TH-immunoreactive fiber and dopamine neuron loss within the nigrostriatal system in each lesioned hemisphere. These results indicate that the interdependent regulation of the two nigrostriatal systems may provide some compensatory support for the function and behavioral performance of the lesioned side via the normal unlesioned side, which is lost in animals with bilateral lesions of the nigrostriatal system. Therefore, this model of uni- and bilateral partial lesions of the nigrostriatal system, as characterized in the present study, may foster further exploration of compensatory functional mechanisms active in the early stages of Parkinson's disease and promote development of novel neuroprotective and restorative strategies.

CD44s-targeted treatment with monoclonal antibody blocks intracerebral invasion and growth of 9L gliosarcoma.

Glioma invasiveness is a complex process involving recognition and attachment of tumor cells to particular extracellular matrix (ECM) molecules prior to migrating into proteolytically modified matrix and inducing angiogenesis. CD44 is a group of transmembrane adhesion molecules found on a wide variety of cells including gliomas that has been suggested as the principal mediator of migration/invasion. The aim of the present study was to demonstrate whether antibody specific for the standard form of CD44 (CD44s, 85-90 kDa) might prevent invasion, thus blocking growth of the 9L gliosarcoma in vivo. High expression of CD44s on the surface of 9L cells and brain tumors was demonstrated by immunochemistry. Fluorescence-activated cell sorting (FACS) demonstrated binding saturation of anti-CD44s monoclonal antibody (mAb) to the receptor at 1 microg/5 x 10(5) cells. Blocking of CD44s in vitro resulted in a dose-dependent progressive, up to 95%+/-2.5% detachment of 9L cells from ECM-coated culture surfaces. Blocking of CD44s in vivo resulted in significantly reduced 9L brain tumors (2.5%+/-0.4%)--measured as the quotient: tumor surface (mm2)/brain surface (mm2) x 100--as compared to untreated (16.1%+/-2.2%) or sham-treated rats (16%+/-3.7% to 16.1%+/-3%). We conclude that CD44s-targeted treatment with specific mAb may be an effective means for preventing glioma progression.

Evidence of recurrent atypical meningioma with rhabdoid transformation and expression of pyrogenic cytokines in a child presenting with a marked acute-phase response: case report and review of the literature.

Children presenting with acute systemic illnesses that lack specific clinical or serological defining features may be diagnosed as having a chronic infection, an atypical systemic vasculitis or a connective tissue disease, but often turn out to have occult neoplasias. Cytokines have been implicated in causing many of the systemic effects in such cases. In this study, we describe the case of a 9-year-old boy presenting at an interval of 18 months with a marked acute-phase response due to a recurrent atypical meningioma with rhabdoid transformation of the tentorium cerebelli. Resection of the recurrent tumor was curative. We evaluated in detail the local and systemic production of cytokines released by the primary and the recurrent tumor. Blood and CSF samples were taken pre-, intra-, and postoperatively, and the production of IL-6, IL-1beta, and TNF-alpha was measured by enzyme-linked immunosorbent assays (ELISA). The level of IL-6 in CSF was about 150-fold increased before tumor resection, normalizing postoperatively. On the contrary, the levels of IL-1beta and TNF-alpha in CSF and of IL-6, IL-1beta, and TNF-alpha in serum were pre-, intra-, and postoperatively within normal limits. Cytokine production was also evaluated immunohistochemically, and confirmed strong IL-6 and TNF-alpha expression in the primary and the recurrent tumor, while expression of IL-1beta was lacking. The scattered MHC class II- and leukocyte common antigen (LCA)-expressing inflammatory cells, which were infiltrating exclusively the tumoral stroma, had no detectable cytokine immunoreactivity. We conclude that chronic IL-6 and TNF-alpha production by the tumor cells in this patient was responsible for the severe systemic illness with which he presented.

Expression of cathepsin K in chordoma.

Invasive growth of chordoma is accompanied by severe destruction of adjacent bone tissue, a fact that requires high proteolytic activity at the tumor invasion fronts. In this context, cathepsin K is a candidate molecule. It is a protease with high collagenolytic and elastinolytic activity and previously thought to be restricted to osteoclasts and osteoclast-mediated bone resorption. In this study, 44 cases of chordoma of sphenooccipital localization, and 10 embryo-fetal specimens including chorda dorsalis were studied immunohistochemically for their expression of cathepsin K. In 4 additional snap-frozen chordoma cases, the enzyme expression was investigated by reverse transcription polymerase chain reaction and enzyme histochemistry. Ten chondrosarcomas of the skull base served as controls. Various concentrations of cathepsin K mRNA could be seen in all snap-frozen chordoma specimens. The protease was immunohistochemically expressed by the tumor cells. The immunoreactions were accentuated at the tumor invasion fronts. Enzyme histochemistry indicated a strong tumor cell-associated cathepsin K activity in invasive tumor components. In contrast to chordoma, cathepsin K was not significantly expressed in chorda dorsalis and chondrosarcoma of the skull base. In chondrosarcoma, protease expression was limited to osteoclastic cells localized between infiltrative tumor components and regular bone trabeculae. This study shows the significant expression and activity of cathepsin K in chordoma and implicates an important and direct role of this protease in the infiltrative growth of this tumor. This protease expression occurred during neoplastic transformation and did not appear in chorda dorsalis.

Current status and future challenges in cerebral blood flow mapping in intracranial tumors.

CBF studies have been applied in patients with cranial tumors using XenonCT in order to evaluate the blood flow of both the tumor and the peritumoral brain tissue. The histology included mostly meningiomas or gliomas, less frequently neurinomas or metastases. Blood flow was determined in tumor tissue (TBF), peritumoral areas (PTBF) and cerebral hemispheres (hCBF). The CBF was compared to normative CBF values. In supratentorial tumors characteristical blood flow patterns were found according to the histology. PTBF was usually lower in edematous tissue than in normal brain tissue. TBF in malignant gliomas revealed a heterogeneous pattern with a central core of low flow and a peripheral zone with high flow. Global CBF values in patients with malignant gliomas were lower than in controls. Meningiomas showed significantly higher blood flow compared to gliomas or neurinomas. In some cases with large cerebellopontine angle tumors a reduction in brain stem blood flow was detected. In cavernous sinus tumors with carotid artery compression CBF and cerebrovascular reserve capacity was not impaired. These findings indicate that tumor induced alterations in cerebral circulation can be detected by CBF mapping. This diagnostic tool offers a further insight into perfusion related tumor pathophysiology and may thereby optimize individual neurooncological treatment strategies.

CBF determination in brain stem and cerebellar hemispheres.

CBF of brain stem and cerebellar hemispheres is of particular significance in different cranial diseases and can be determined by PET, SPECT and XenonCT. We have used XenonCT CBF method to study 78 patients with posterior fossa tumors or cerebrovascular disorders. A retrospective analysis of the first 56 CBF studies showed that bone artifacts were the most common cause of study failure. Based on these experiences we have developed a protocol to study brain stem and cerebellar blood flow. Because bone artifacts significantly degrade flow information, we obtained images over the petrous bone with a CT gantry angle of approximately 25 degrees to the orbitomeatal line. The failure rate could be reduced from 41% to 13% with this study protocol. Brain stem blood flow determination may help to clarify the prognosis in head trauma patients and show more physiological details in tumors of the posterior fossa. The phenomenon of crossed cerebellar diaschisis in cerebral insults or neoplasms can be investigated by XenonCT easily.

Direct magnification technique for cerebral angiography in the rat.

RATIONALE AND OBJECTIVES: The authors evaluated the performance of direct magnification radiography (DIMA) with digital image processing for cerebral angiography in the rat. METHODS: A microfocal x-ray unit with a focal spot of 5 microns was used for cerebral angiography in 10 rats. The animals were examined form x 4 up to x 20 magnification after injection of 0.2 mL x-ray contrast medium into the common carotid artery. RESULTS: Direct magnification radiography technology provides high resolution images and enables the visualization of very small vessels with high quality. It allows the peripheral branches of the middle cerebral artery or the ophthalmic artery to be visualized. Superimposition and noise effects can be excluded with digital subtraction and image processing. CONCLUSIONS: The experiments show that DIMA radiography is a suitable technique for cerebral angiography in the rat.

Cerebral metabolic response to traumatic brain injury sustained early in development: a 2-deoxy-D-glucose autoradiographic study.

Following fluid percussion (FP) traumatic brain injury (TBI), adult rats exhibit dynamic regional changes in cerebral glucose metabolism characterized by an acute (hours) increase and subsequent chronic (weeks) decrease in metabolic rates. The injury-induced hyperglycolysis is the result of ionic fluxes across cell membranes and the degree and extent of metabolic depression is predictive of neurobehavioral deficits. Given that younger animals appear to exhibit similar physiological responses to injury yet show an improved rate of recovery compared to adults, we wanted to determine if this injury-induced dynamic metabolic response to TBI is different if the injury is sustained early in life. Local cerebral metabolic rates for glucose (ICMRglc: micromol/100 g/min) using [14C]2-deoxy-D-glucose were measured immediately, 30 min, 1 day, and 3 days following a mild to moderate level of lateral FP injury in postnatal day 17 (P17) rats. Even though gross morphological damage was not evident, injured pups exhibited ipsilateral hyperglycolysis immediately after injury, predominantly in cortical regions (ranging from 59.2% to 116.5% above controls). This hyperglycolytic state subsided within 30 min, and by 1 day all cerebral structures, except the ipsilateral cerebellar cortex, showed lower rates of glucose metabolism (ranging from 5.7% to 63.0% below controls). This period of posttraumatic metabolic depression resolved within 3 days for all structures measured. Compared to previous adult studies these results suggest that the young rat pup, although exhibiting acute hyperglycolysis, is not subjected to a prolonged period of metabolic depression, which supports the findings that at this level of injury severity, these young animals show remarkable neurological sparing following TBI.

Immunohistochemical characterization of axonal sprouting and reactive tissue changes after long-term implantation of a polyimide sieve electrode to the transected adult rat sciatic nerve.

The development of artificial microstructures suited for interfacing of peripheral nerves is not only relevant for basic neurophysiological research but also for future prosthetic approaches. Aim of the present study was to provide a detailed analysis of axonal sprouting and reactive tissue changes after implantation of a flexible sieve electrode to the proximal stump of the adult rat sciatic nerve. We report here that massive neurite growth after implantation, steadily increasing over a period of 11 months, was observed. Parallel to this increase was the expression of myelin markers like Po, whereas non-myelin-forming Schwann cells did not change. Compared to five weeks post-implantation. where both Schwann-cell phenotypes were intermingled with each other, non-myelin-forming Schwann cells occupied a peripheral position in each microfascicle after 11 months. After an initial increase, hematogenous macrophages were down-regulated in number but maintained close contact with the implant. However, at no time were signs of its degradation observed. It is concluded that the introduced flexible polyimide electrode is suitable for contacting peripheral nerves since it permits substantial neurite growth and offers excellent long-term stability.

The prognostic value of progesterone receptor status in meningiomas.

BACKGROUND: Meningiomas are known to recur frequently, and their longterm management remains controversial. Previous studies indicate that progesterone and its receptors can play a role in the recurrence of meningiomas, but the correlation between the presence of these receptors and patients' outcome is unclear. AIM: To conduct a retrospective analysis to investigate the prognostic relevance of progesterone receptor (PR) expression in meningiomas. METHODS: Five hundred and eighty eight meningiomas operated on over a period of 10 years were examined immunohistochemically to determine the PR status using monoclonal antibodies. Several factors including recurrence (mean follow up of 65 month), sex, tumour tissue consistency, location, vascularity, and en plaque appearance were analysed. RESULTS: PR status showed comparable values for men and women. World Health Organisation (WHO) grade II and III tumours had significantly fewer receptors than benign meningiomas. There was no significant correlation between PR status and recurrence rates in WHO grade I totally removed meningiomas. However, a combination of PR status and proliferation indices was shown to predict recurrence reliably. CONCLUSIONS: Together with routine histological evaluation, PR status can help to describe the biological behaviour of meningiomas. Only a combination of clinical and biological features can describe the behaviour of meningiomas, predict their recurrence, and help to devise more effective follow up strategies.

Regeneration of a transected peripheral nerve by transplantation of spinal cord encapsulated in a vein.

The objective was to investigate the regeneration of a transected peripheral nerve after transplantation of fragmented embryonic (E14-15) spinal cord cells which were encapsulated within a vein cavity. After 3 months transplantation, axonal regeneration was observed by staining with HE and antibody to neurofilament subtypes in six of 10 rats. In all six animals compound muscle action potentials to electrical stimulation could be recorded and indicated incomplete reinnervation of the fibular and tibial nerve, respectively. A chronic inflammation process around the transplant and a negative result of staining neurofilaments within the vein cavity and the transected nerve were found in animals lacking electrophysiological response to stimulation.

Complex sensorimotor behavioral changes after terminal striatal 6-OHDA lesion and transplantation of dopaminergic embryonic micrografts.

In this study sensorimotor behavioral changes were monitored in rats following bilateral 6-hydroxydopamine (6-OHDA) axon terminal lesion and uni- or bilateral implantation of embryonic dopaminergic (DA) micrografts. A total of 28 microg of 6-OHDA was distributed over four injection tracts in the dorsolateral part of the caudate-putamen (CPU) bilaterally followed 4 months later by the implantation of DA micrografts spread over seven implantation tracts placed within the denervated area. Bilaterally 6-OHDA-lesioned animals exhibited significantly reduced behavioral performance scores in tests of explorational and stepping behavior as well as in skilled forelimb use. However, in contrast to the established medial forebrain bundle (MFB) lesion model of PD, these animals showed a spontaneous recovery in the side falling and skilled forelimb behavior and no deficits in overnight locomotor activity at 6 months after the lesion. Unilateral DA micrografts elicited a substantial amphetamine-induced rotational bias contralateral to the graft, but led to a significant impairment of contralateral skilled forelimb use and reduced scores in overnight locomotor activity. Bilateral DA micrografts caused a significant, though partial, increase in explorational and backhand stepping behavior, but resulted also in a significant decrease in performance levels in overnight locomotor activity and skilled forelimb use on both paws. In conclusion, DA grafts placed ectopically in the CPU in the partial lesion model of PD result in a double innervation of the GABAergic striatal neurons, arising from the residual nigrostriatal DA projections of the host and from the graft-derived DA efferent fibers. These two DA fiber systems may indeed function in a cooperative and competitive manner depending on their respective and different afferent and efferent connections, which, in turn, may lead to positive or negative influences on basal ganglia function and behavioral performances. The different patterns of 6-OHDA lesion and transplant-induced behavioral changes demonstrated in the present study compared to the "classical" MFB lesion model of PD may thus provide further insights in the complex functional organization of the basal ganglia and, thereby, may help to further optimize restorative strategies for neurodegenerative diseases, such as Parkinson's disease.

Differences in acquisition and full performance in skilled forelimb use as measured by the 'staircase test' in five rat strains.

Skilled forelimb use was examined in five different rat strains (DA/Ztm, LEW/Ztm-ci, LEW.1W/Ztm, SD/Ztm, SPRD/Ztm-Cu3) by means of the 'staircase test', as originally described by Montoya et al. [20] (C.P. Montoya, H.L. Campbell, K.D. Pemberton, S.B. Dunnett, The 'staircase test': A measure of independent forelimb reaching and grasping abilities in rats, J. Neurosci. Methods 36 (1991) 219-228). Strain-dependent differences were observed most prominently during the acquisition phase, and less pronounced, at the full performance level. SD/Ztm and DA/Ztm rat strains seemed to be particularly skilled in their forelimb use, although with varying levels of activity. Interestingly, significant differences in skilled forelimb movements were found between the related Sprague-Dawley derived and Lewis congenic rat strains. No clear-cut correlation was found between skilled forelimb use and basic nutrition-dependent measures, such as pretest body weight or weightloss during the test period. Based on previous observations on strain-dependent behavioral variations it seems likely that the differences in skilled forelimb use, as observed in the present study, might be caused by morphological and/or functional strain-dependent alterations in the involved neuronal circuitries, such as motor cortex, caudate-putamen unit and mesotelencephalic dopamine system. However, they should also be considered as potentially influencing parameters in studies related to the behavioral effects of lesions and restorative therapies in the central nervous system.

Hemispheric asymmetries in spontaneous firing characteristics of substantia nigra pars reticulata neurons following a unilateral 6-hydroxydopamine lesion of the rat nigrostriatal pathway.

Single unit activity of substantia nigra pars reticulata (SNR) neurons was recorded bilaterally in rats subjected to unilateral 6-hydroxydopamine lesions of the ascending mesostriatal dopaminergic pathway, resulting in an almost complete loss of dopaminergic neurons in the ipsilateral SN pars compacta. Firing rate and firing pattern of SNR neurons in lesioned rats were compared with respective data from sham-lesioned rats and naive controls. In lesioned rats, the mean firing rate of SNR neurons at the lesioned side was significantly reduced and there was an increase in the occurrence of bursting activity. In contrast, firing rate in the contralateral SNR was significantly increased without change in the frequency of bursting neurons. This asymmetrical change in spontaneous firing characteristics of SNR neurons following the lesion could be involved in the complex behavioral changes seen in this model of Parkinson's disease.