Metabolism in the globus pallidus after fetal implants in rats with nigral lesions

1993 ◽  
Vol 78 (1) ◽  
pp. 83-89 ◽  
Author(s):  
Howard M. Eisenberg ◽  
Massako Kadekaro ◽  
Sondra Freeman ◽  
Mary Lee Terrell

✓ The effect of fetal mesencephalic implants on glucose utilization in selected brain structures and on apomorphine-induced rotational behavior was measured in rats with a unilateral lesion of the substantia nigra. Ipsilateral, but not contralateral, implants decreased the rotational behavior induced by apomorphine. In addition, the nigral lesion decreased glucose utilization in the dorso- and ventrolateral quadrants of the striatum and in the entopeduncular nucleus but increased glucose utilization in the ipsilateral globus pallidus and lateral habenula. The increased metabolism in the globus pallidus was attenuated by ipsilateral, but not contralateral, mesencephalic implants which also decreased glucose utilization in the dorsomedial caudate nucleus. These results indicate that the ability of an ipsilateral mesencephalic graft to ameliorate the motor behavior in rats with nigral lesions is associated with changes in the functional activity of the ipsilateral globus pallidus.

2004 ◽  
Vol 100 (6) ◽  
pp. 997-1001 ◽  
Author(s):  
Mitsuhiro Ogura ◽  
Naoyuki Nakao ◽  
Ekini Nakai ◽  
Yuji Uematsu ◽  
Toru Itakura

Object. Although chronic electrical stimulation of the globus pallidus (GP) has been shown to ameliorate motor disabilities in Parkinson disease (PD), the underlying mechanism remains to be clarified. In this study the authors explored the mechanism for the effects of deep brain stimulation of the GP by investigating the changes in neurotransmitter levels in the cerebrospinal fluid (CSF) during the stimulation. Methods. Thirty patients received chronic electrical stimulation of the GP internus (GPi). Clinical effects were assessed using the Unified PD Rating Scale (UPDRS) and the Hoehn and Yahr Staging Scale at 1 week before surgery and at 6 and 12 months after surgery. One day after surgery, CSF samples were collected through a ventricular tube before and 1 hour after GPi stimulation. The concentration of neurotransmitters such as γ-aminobutyric acid (GABA), noradrenaline, dopamine, and homovanillic acid (HVA) in the CSF was measured using high-performance liquid chromatography. The treatment was effective for tremors, rigidity, and drug-induced dyskinesia. The concentration of GABA in the CSF increased significantly during stimulation, although there were no significant changes in the level of noradrenaline, dopamine, and HVA. A comparison between an increased rate of GABA concentration and a lower UPDRS score 6 months postimplantation revealed that the increase in the GABA level correlated with the stimulation-induced clinical effects. Conclusions. Stimulation of the GPi substantially benefits patients with PD. The underlying mechanism of the treatment may involve activation of GABAergic afferents in the GP.


1999 ◽  
Vol 90 (5) ◽  
pp. 928-934 ◽  
Author(s):  
Daniel M. Lieberman ◽  
Marc-Etienne Corthesy ◽  
Alex Cummins ◽  
Edward H. Oldfield

Object. Symptoms from Parkinson's disease improve after surgical ablation of the medial globus pallidus (GPm). Although, in theory, selective chemical ablation of neurons in the GPm could preserve vital structures jeopardized by surgery, the potential of this approach is limited when using traditional techniques of drug delivery. The authors examined the feasibility of convection-enhanced distribution of a neurotoxin by high-flow microinfusion to ablate the neurons of the GPm selectively and reverse experimental Parkinson's disease (akinesia, tremor, and rigidity).Methods. Initially, to test the feasibility of this approach, the GPms of two naive rhesus macaques were infused with kainic acid or ibotenic acid through two cannulas that had been placed using the magnetic resonance imaging—guided stereotactic technique. Two weeks later the animals were killed and their brains were examined histologically to determine the presence of neurons in the GPm and the integrity of the optic tract and the internal capsule. To examine the therapeutic potential of this paradigm, unilateral experimental Parkinson's disease was induced in six macaques by intracarotid infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and their behavior was studied for 12 weeks after chemopallidotomy was performed using kainic acid (three animals) or control infusion (three animals).Conclusions. Chemopallidotomy using kainic acid permanently reversed the stigmata of MPTP-induced parkinsonism. By contrast, the control animals exhibited a transient recovery following intrapallidal infusion and then relapsed back to their baseline state. The use of high-flow microinfusion of selectively active toxins has the potential for treatment of Parkinson's disease and, by expanding the range of approachable targets to include large nuclei, for broad applications in clinical and experimental neuroscience.


2005 ◽  
Vol 102 (4) ◽  
pp. 664-672 ◽  
Author(s):  
Kyousuke Kamada ◽  
Tomoki Todo ◽  
Yoshitaka Masutani ◽  
Shigeki Aoki ◽  
Kenji Ino ◽  
...  

Object. The aim of this study was better preoperative planning and direct application to intraoperative procedures through accurate coregistration of diffusion-tensor (DT) imaging—based tractography results and anatomical three-dimensional magnetic resonance images and subsequent importation of the combined images to a neuronavigation system (functional neuronavigation). Methods. Six patients with brain lesions adjacent to the corticospinal tract (CST) were studied. During surgery, direct fiber stimulation was used to evoke motor responses to confirm the accuracy of CST depicted on functional neuronavigation. In three patients, stimulation of the supposed CST elicited the expected motor evoked potentials. In the other three, stimulation at the resection borders more than 1 cm away from the supposed CST showed no motor response. All patients underwent appropriate tumor resection with preservation of the CST. Conclusions. Integration of the DT imaging—based tractography information into a traditional neuronavigation system demonstrated spatial relationships between lesions and the CST, allowing for the avoidance of tract injury during lesion resection. Direct fiber stimulation was used for real-time reliable white matter mapping, which served to adjust for any discrepancy between the neuronavigation system data and potentially shifted positions of the brain structures. The combination of these techniques enabled the authors to identify accurate positions of the CST during surgery and to accomplish optimal tumor resections.


2004 ◽  
Vol 100 (1) ◽  
pp. 68-72 ◽  
Author(s):  
Ryuta Suzuki ◽  
Jun-ichiro Asai ◽  
Goro Nagashima ◽  
Hiroshi Itokawa ◽  
Chih-Wei Chang ◽  
...  

Object. Transsphenoidal surgery for the removal of macroadenomas has some disadvantages, including the risk of performing procedures without adequate visualization, difficulties in estimating the amount of residual tumor, and the risk of injuring major vessels. To overcome these disadvantages, the authors have developed transcranial echo-guided transsphenoidal surgery. Methods. Three patients with large macroadenomas and two patients with irregularly shaped macroadenomas were selected for this operation. In addition to standard preparations for transsphenoidal surgery, in each case the right frontal bone was trephined and an echo probe was inserted transdurally through the trephination hole. During tumor removal, brightness-mode echo images and Doppler color flow images were obtained. The echo images allowed for real-time visualization of the tumor and surrounding brain structures including major arteries and the cisterns; histological heterogeneities of the tumor could also be appreciated. The tumors were removed safely and maximal tumor removal was achieved. Conclusions. Transcranial echo-guided transsphenoidal surgery provides real-time visualization of tumor removal. The method enhances the safety of this surgery, maximizes the removal of the tumor, and is inexpensive.


2004 ◽  
Vol 101 (2) ◽  
pp. 189-194 ◽  
Author(s):  
Philippe Coubes ◽  
Laura Cif ◽  
Hassan El Fertit ◽  
Simone Hemm ◽  
Nathalie Vayssiere ◽  
...  

Object. Primary generalized dystonia (PGD) is a medically refractory disease of the brain causing twisting or spasmodic movements and abnormal postures. In more than 30% of cases it is associated with the autosomal DYT1 mutation. Continuous electrical stimulation of the globus pallidus internus (GPi) has been used successfully in the treatment of PGD. The aim of this study was to examine the long-term efficacy and safety of deep brain stimulation (DBS) in the treatment of PGD in children and adults with and without the DYT1 mutation. Methods. Thirty-one patients with PGD were selected for surgery. Electrodes were bilaterally implanted under stereotactic guidance and connected to neurostimulators that were inserted subcutaneously. Efficacy was evaluated by comparing scores on the clinical and functional Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) before and after implantation. The efficacy of stimulation improved with time. After 2 years, compared with preoperative values, the mean (± standard deviation) clinical and functional BFMDRS scores had improved by 79 ± 19% and 65 ± 33%, respectively. At the 2-year follow-up examination the improvement was comparable in patients with and without the DYT1 mutation in both the functional (p = 0.12) and clinical (p = 0.33) scores. Children displayed greater improvements in the clinical score than adult patients (p = 0.04) at 2 years of follow up. In contrast, there was no significant difference in functional scores between children and adults (p = 0.95). Conclusions. Electrical stimulation of the GPi is an effective, reversible, and adaptable treatment for PGD and should be considered for conditions refractory to pharmaceutical therapies.


2004 ◽  
Vol 101 (6) ◽  
pp. 895-903 ◽  
Author(s):  
A. John Popp

✓ The concept of musical genius used to frame a discussion of the “art” practiced by neurosurgeons is the focus of the 2004 Presidential Address to the American Association of Neurological Surgeons (AANS). The musical genius, in contrast to the musically talented individual, is profiled and placed in the pantheon of those who have demonstrated extraordinary creativity. Observations and speculations about the specialization and elaboration of brain structures in musicians evolve into a discussion of artificial intelligence as a foil to what constitutes the essence of humanity. Taking an inductive approach, the author juxtaposes the conclusion about “music, musicians, and the brain” with the theme of the 2004 annual meeting of the AANS, “Advancing Patient Care Through Technology and Creativity,” to elaborate on the characteristics of the consummate neurosurgeon. (Note: Musical vignettes used in the address can be found in the accompanying article posted on Neurosurgical Focus http://www.aans.org/education/journal/neurosurgical).


1994 ◽  
Vol 80 (3) ◽  
pp. 491-501 ◽  
Author(s):  
Paul D. Chumas ◽  
James M. Drake ◽  
Marc R. Del Bigio ◽  
Marcia Da Silva ◽  
Ursula I. Tuor

✓ The metabolic changes in neonatal hydrocephalus that lead to permanent brain injury are not clearly defined, nor is the extent to which these changes can be prevented by a cerebrospinal fluid shunt. To clarify these processes, cerebral glucose utilization was examined using [14C]2-deoxyglucose autoradiography in 1-month-old kittens, kaolin-induced hydrocephalic littermates, and hydrocephalic kittens in which a ventriculoperitoneal shunt had been inserted 10 days after kaolin injection. The hydrocephalic kittens showed thinning of the cerebral mantle and an anterior-to-posterior gradient of enlargement of the ventricular system, with a ventricle:brain ratio of 24% for the frontal and 35% for the occipital horns compared with control (< 0.5%) and shunted (< 5%) animals. White matter in hydrocephalic animals was edematous. Myelination was delayed in the periventricular region and in the cores of the cerebral gyri. Glucose utilization in hydrocephalic and shunted animals was unchanged from control animals in all gray-matter regions examined. However, in hydrocephalic animals, the frontal white matter exhibited a significant increase in glucose utilization (25 µmol • 100 gm−1 • min−1) in the cores of gyri compared with normal surrounding white-matter values (14.8 µmol • 100 gm−1 • min−1). Very low values (mean 4 µmol • 100 gm−1 • min−1) were found in areas corresponding to severe white-matter edema, and these areas were surrounded by a halo of increased activity (24 µmol • 100 gm−1 • min−1). In contrast, cytochrome oxidase activity in white matter was homogeneous. Shunting resulted in restoration of the cerebral mantle thickness, a return to normal levels of glucose utilization in the white matter, and an improvement in myelination. It is suggested that the areas of increased glucose utilization seen in the white matter represent anaerobic glycolysis which, if untreated, progresses to infarction. The pattern of this increased glucose utilization matches that of expected myelination and, during this period of high energy demand, white matter may be susceptible to the hypoperfusion associated with hydrocephalus.


1991 ◽  
Vol 74 (6) ◽  
pp. 1009-1010 ◽  
Author(s):  
Takeshi Hasegawa ◽  
Kiyotoshi Yamano ◽  
Tadao Miyamori ◽  
Yoshitaka Hamada

✓ A new microsurgical device for delicate brain retraction is described. The device, a micromanipulator with a holder for a brain spatula fixed at the end of a self-retaining retractor arm, allows smooth, steady, fine displacement of the retractor tip (“minimal sliding retraction”), operated by the surgeon's two fingers. This has proved to be a useful and safe method of retraction for critical brain structures such as blood vessels, cranial nerves and aneurysm domes in deep microsurgical fields.


1999 ◽  
Vol 91 (1) ◽  
pp. 109-113 ◽  
Author(s):  
Christopher R. Honey ◽  
Hao Shen

Object. The goal of this study was to compare the effects of short- and long-term immunosuppression induced by cyclosporin with those of immunosuppression induced by a monoclonal antibody against the rat interleukin-2 receptor (anti-CD25 mAb) in rats with xenografts.Methods. The authors compared the in vivo function and final histological characteristics of fetal mouse mesencephalon xenografts in hemiparkinsonian rats in which immunosuppression was induced by: 1) a short course (2 weeks) of cyclosporin; 2) a long course (8 weeks) of cyclosporin; or 3) a short course of treatment with anti-CD25 mAb. Adult Wistar rats were unilaterally lesioned with 6-hydroxydopamine in their medial forebrain bundle, after which their rotational behavior in response to methamphetamine was quantified. Four groups of 20 rats with rotations numbering greater than six turns per minute received fetal mouse mesencephalon transplants to their dopamine-denervated striatum. Group 1 received no immunosuppression therapy; Group 2 received daily intraperitoneal injections of 10 mg/kg cyclosporin for 2 weeks; Group 3 received daily intraperitoneal injections of 10 mg/kg cyclosporin for 8 weeks; and Group 4 received daily intraperitoneal injections of 1 mg/kg anti-CD25 mAb for 2 weeks. The rats were tested for rotational behavior every 4 weeks and killed after 16 weeks. Surviving xenografts were assessed using immunohistochemical staining for a mouse neuronal marker (Thy-1.2). Sixteen weeks after transplant, there were significantly more surviving xenografts in Groups 3 (p < 0.001) and 4 (p < 0.001) compared with control Group 1 (Fisher's exact test) and significantly better functioning xenografts in Groups 3 (p < 0.01) and 4 (p < 0.05) compared with control Group 1 (contrasts of groups following analysis of variance with Bonferroni correction).Conclusions. A short course of anti-CD25 mAb—induced immunosuppression was as effective as a long course of cyclosporin-induced immunosuppression in this model.


1982 ◽  
Vol 57 (4) ◽  
pp. 543-547 ◽  
Author(s):  
George Tyson ◽  
Paul Kelly ◽  
James McCulloch ◽  
Graham Teasdale

✓ Choroid plexus blood flow (CPBF) and glucose utilization (CPGU) were measured in two groups, each of seven identically prepared, unanesthetized rats, using complementary quantitative autoradiographic techniques. Both CPBF and CPGU were lowest in the lateral ventricles (0.83 ± 0.01 ml · g−1 · min−1 and 0.70 ± 0.02 µmoles · g−1 · min−1, respectively) and highest in the fourth ventricle (1.56 ± 0.05 ml · g−1 · min−1 and 1.39 ± 0.05 µmoles · g−1 · min−1, respectively). Despite this heterogeneity, the proportionate relationship between CPBF and CPGU was relatively constant throughout the ventricular system. This suggests that blood flow and metabolism may normally be coupled in the choroid plexus, and that the choroid plexus of the fourth ventricle may account for a disproportionate share of the functional activity of this tissue.


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