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At least 37 records · Page 2Linked to original sources

Single or continuous injection of glial cell line-derived neurotrophic factor in the striatum induces recovery of the nigrostriatal dopaminergic system.

Glial cell line-derived neurotrophic factor (GDNF) is a member of the transforming growth factor beta superfamily and acts as a neurotrophic factor for the nigrostriatal dopaminergic system. GDNF at a dose of 100 micrograms was injected stereotactically into the striatum of Sprague-Dawley rats that had been treated with intrastriatal 6-hydroxydopamine (6-OHDA) injection four weeks earlier. Immunocytochemical and behavioral analyses showed significant recovery of the nigrostriatal dopaminergic system after a single GDNF injection or continuous GDNF injection. Immunocytochemical and behavioral study showed that there was no significant difference between the results obtained from the two different injection methods. This result demonstrates the potential usefulness of GDNF for the treatment of Parkinson's disease.

Animals↗

[Neurosurgical therapy for parkinson's disease].

Stereotactic surgery and neuronal transplantation are considered to be effective surgical therapies for advanced Parkinson's disease with wearing off phenomenon. As a stereotactic surgery, posteroventral pallidotomy and chronic pallidal or subthalamic stimulation with inhibitory parameters were performed. Flattening of the motor fluctuations were obtained with improving general motor symptoms especially at "off" time. Therapeutic l-dopa dose could not reduced following pallidotomy and pallidal stimulation, whereas subthalamic stimulation saved 30-50% of l-dopa dose. By the constant supply of dopamine, neuronal transplantation was effective on wearing off. Chromaffin cells of adrenal medulla and pretransected peripheral nerve were cografted into the bilateral caudate nuclei. After the transplantation significant reduction of % time off and l-dopa dose was observed.

Adrenal Medulla↗

Neural transplantation for Parkinson's disease.

1. Neural transplantation is one promising approach for the treatment of Parkinson's disease. Fetal substantia nigra cells are a good source of dopamine, but in order to avoid ethical and immunological problems, adrenal medullary chromaffin cells have been investigated as an alternative source. 2. Grafted adrenal medullary chromaffin cells can provide dopamine as well as several neurotrophic factors that affect dopaminergic neurons in the brain. 3. We review experimental studies for application of neural transplantation techniques in Parkinson's disease, including immunological studies, cryopreservation, microvasculature, donor tissue, and direct gene delivery studies performed in our laboratory. Our clinical experience and new approach involving a polymer-encapsulated cell grafting procedure are also described.

Animals↗

A giant thrombosed aneurysm of the petrous carotid artery presenting with cavernous sinus syndrome: case report.

Aneurysms involving the petrous Carotid artery are rare and a review of the literature demonstrates that the mode of clinical presentation depends on the direction of expansion of the aneurysmal sac. The eighth nerve is the most commonly affected, followed by the fifth nerve, sixth nerve and seventh nerve, respectively. There has not been reported to date a lesion presenting with cavernous sinus syndrome. We present the case of a 46-year-old woman who complained of left facial pain and pan-ophthalmoplegia, and was shown to have a giant thrombosed aneurysm of the petrous carotid artery extending into the cavernous sinus. Because preoperative evaluation of the patient revealed good collateral flow, proximal balloon occlusion of the left internal carotid artery was performed. Neurological symptoms of the patient resolved 2 months after surgery except for the size of the left pupil. We conclude that an aneurysm of the petrous carotid artery should be included in the differential diagnosis of cases presenting with a cavernous sinus syndrome. Early diagnosis followed by definitive treatment is important for the alleviation of clinical symptoms associated with this lesion.

Case Reports↗

GDNF administration induces recovery of the nigrostriatal dopaminergic system both in young and aged parkinsonian mice.

Glial cell line-derived neurotrophic factor (GDNF) is a member of the transforming growth factor beta superfamily and acts as a neurotrophic factor for the nigrostriatal dopaminergic system. GDNF was injected stereotaxically into the striatum of young (2 months old) and aged (12 months old) C57BL/6 mice that were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) 1 week earlier. Immunocytochemical and neurochemical analyses showed significant recovery of the nigrostriatal dopaminergic system both in young and in aged mice. Since Parkinson's disease is a neurodegenerative disorder mainly affecting elderly people, this result demonstrates the potential usefulness of GDNF in treating Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Decoy administration of NF-kappaB into the subarachnoid space for cerebral angiopathy.

Subarachnoid hemorrhage (SAH), encephalitis, meningitis, and autoimmune diseases sometimes lead to cerebral angiopathy, characterized specifically by narrowing of vessels, morphological changes in the structure of vessel walls, and a concomitant decrease in cerebral blood flow. Many patients also develop delayed ischemic neurological deficits. Thus, preventing vascular reactions is of paramount importance in treating SAH. Although cerebral vasospasm has some relationship with the inflammatory reaction of major cerebral vessels against the autologous blood, and many trials have attempted to prevent angiopathy after SAH, an effective treatment has not yet been established. The purpose of this article is to evaluate the preventive effect of nuclear factor KB (NF-kappaB) decoy oligo-DNA after SAH; since NF-kappaB is closely related to inflammation. In the rabbit angiopathy model after SAH, we evaluated the effectiveness of the decoy oligo-DNA using the angiographic (digital subtraction angiography) and histological (hematoxylin-eosin and Masson's trichrome staining) methods. Moreover, a gel-shift assay for NF-kappaB was also performed in order to evaluate the activity of NF-kappaB. We describe a new concept for treating cerebral angiopathy after SAH and for successfully inhibiting cerebral vasospasm and morphological changes in vessel walls in a rabbit model. In this treatment, we used synthetic double-strand oligo-DNA with a high affinity for transcription factor NF-kappaB, and cationic liposome complex administered through the cerebrospinal fluid.

Animals↗

Significant behavioral recovery in Parkinson's disease model by direct intracerebral gene transfer using continuous injection of a plasmid DNA-liposome complex.

As an alternative to virus-mediated gene transfer, we previously demonstrated a simple, safe, and efficient transfer of foreign gene into the central nervous system using continuous injection of a plasmid DNA-cationic liposome complex. To explore whether this approach can be applied to the treatment of certain neurological disorders, we used an experimental model of Parkinson's disease (PD) in the present study. Following continuous injection for 7 days, tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) genes carried by a bovine papilloma virus-based plasmid vector were efficiently introduced into glial cells in the striatum of 6-hydroxydopamine-lesioned rats. Significant recovery in apomorphine-induced rotational behavior of PD models was obtained by transfection of TH gene and this effect continued for up to 5 weeks after injection. Moreover, cotransfection of TH with AADC genes was readily accomplished by this procedure and resulted in a greater and longer-lasting improvement of apomorphine-induced rotational behavior than was achieved by transfection of TH gene alone. We suggest that this approach is a controllable and manageable alternative to other methods of gene therapy for the treatment of PD.

Animals↗

In vivo gene transfer into the adult mammalian central nervous system by continuous injection of plasmid DNA-cationic liposome complex.

Previously reported methods of liposome-mediated direct in vivo gene transfer have been inefficient, especially when performed with highly differentiated, quiescent cells of the adult mammalian central nervous system (CNS). We have therefore improved these procedures based upon a novel concept. Following continuous injection of plasmid DNA-cationic liposome complex which contained a reporter gene encoding E. coli beta-galactosidase into the striatum of adult rats, the expression of transgene was dramatically elevated without any adverse effects. This new technique may enable a wide application of liposome-mediated gene transfer technology not only to basic analysis of gene functions in the brain but also for clinical treatment of certain CNS disorders.

Animals↗

"Kissing" bilateral large carotid-ophthalmic aneurysms. A case report.

A case of unruptured bilateral large carotid-ophthalmic aneurysms, which appear to be adjoining and "kissing" each other when visualized by three-dimensional computed tomographic angiography (3-D CTA), is reported. Although bilateral carotid-ophthalmic aneurysms are not rare, bilateral large ones are quite rare, and direct imaging of "kissing aneurysms" of this portion has not been reported. Since 3-D CTA is becoming a useful tool for the diagnosis of cerebral aneurysms, we propose that these and similar bilateral large carotid-ophthalmic aneurysms are good candidates for the term "kissing aneurysms".

Aged↗

Cerebral aneurysms causing visual symptoms: their features and surgical outcome.

Cerebral aneurysms causing visual symptoms before surgery are relatively rare. We have experience with 17 cases of such aneurysms and report their clinical features and surgical outcome. The locations of aneurysms presenting with visual dysfunction in our series are as follows: internal carotid (IC)-cavernous aneurysms in six of 29 total cases, 21%; IC-ophthalmic aneurysms in nine of 36 total cases, 25%; and anterior communicating artery (A com A) aneurysms in two of 217 total cases, 1%. The size of the aneurysms, the period between the onset of symptoms and surgical treatment, the pre- and post-operative visual function, and the surgical methods used to treat the aneurysm were analyzed. All the visually symptomatic cases featured large (15-24 mm) or giant (> 25 mm) aneurysms. Visual symptoms occurred before aneurysmal rupture in all cases but one. The type of visual field defect and the degree of reduced visual acuity were highly variable, without a typical clinical presentation. Five out of six IC-cavernous aneurysms were treated surgically with common carotid artery (CC) ligation or IC ligation with superficial temporal artery (STA) to middle cerebral artery (MCA) anastomosis. Three of these cases showed improvement of visual symptoms after surgery. Six out of nine IC-ophthalmic aneurysms were treated surgically (CC ligation or direct clipping), with four cases showing improvement of visual symptoms after surgery. One case of an A com A aneurysm featured a ruptured aneurysm that had physically penetrated the optic chiasm, while the other case was a giant unruptured aneurysm. The interval between the onset of symptoms and surgical treatment was the only factor identified which affected the clinical outcome of the aneurysms presenting with visual dysfunction. All cases that were determined to show improvement of visual function were treated surgically within 3 months of the onset of symptoms. Cerebral aneurysms presenting with visual dysfunction before surgery are most commonly large or giant, and unruptured. Recovery of visual function can most often be expected when surgical treatment is performed expeditiously, before the visual dysfunction becomes irreversible.

Adult↗

Tips for preventing cerebrospinal fluid rhinorrhea after acoustic neurinoma surgery: technical note.

CSF rhinorrhea is a common complication of acoustic neurinoma surgery via the suboccipital route. In this paper we present our incidence of CSF rhinorrhea and our surgical techniques for reducing the risk of this post-surgical complication. Following removal of the acoustic neurinoma, the drilled posterior wall of the internal auditory canal is covered with bonewax, muscle or fat pieces, and fibrin-glue, while the previously reflected dura is sutured in place keeping the packing material in position. Bone chips removed during the craniectomy are then mixed with fibric glue and are used for a cranioplasty. Although we routinely perform aggressive drilling of internal auditory canal to facilitate total removal of the acoustic neurinoma, only 1 out of 94 consecutive cases (1%) showed postoperative CSF rhinorrhea. Since previous reports mention the rate of this complication following acoustic neurinoma surgery varies between 4% and 27%, we believe that our methods may be useful in helping reduce the incidence of postoperative rhinorrhea.

Journal Article↗

Long-term outcome of surgical treatment of intracavernous giant aneurysms.

A number of approaches have been proposed for the treatment of intracavernous giant aneurysms. In the present study, we have analyzed long-term surgical outcome of 27 consecutive cases of our experience. All the cases were unruptured and symptomatic, showing symptoms such as extraocular movement disorder or visual disturbances. Thirteen cases were male and 14 cases were female. The age of the patients ranged between 11 and 75 years (average 52.2 years) and follow-up periods were between 1 and 20 years (average 7.7 years). Abducens nerve was distributed in 20 cases, oculomotor nerve in 12 cases, optic nerve in six cases, trigeminal nerve in six cases, and trochlear nerve in five cases. In addition to conventional angiography, three-dimensional computed tomographic angiography, balloon test occlusion (BTO), slow injection angiography, aneurysmography, and single photon emission computed tomography with BTO were used to determine a method of treatment. Therapeutic modalities of the present series were as follows: four cases were unoperated, common carotid artery ligation was performed in eight cases, internal carotid artery (IC) ligation in three cases, IC ligation plus superficial temporal artery (STA)--middle cerebral artery (MCA) anastomosis in four cases, IC ligation plus high flow vein bypass in three cases, IC trapping plus STA-MCA anastomosis in three cases, and direct clipping in two cases. Although two cases showed early and late ischemic complications, other cases demonstrated improvement of cranial nerve dysfunction relatively soon after surgical treatment and long-term outcome was generally good. It is concluded that good long-term surgical outcome is obtained for intracavernous giant aneurysms by selecting adequate surgical treatment based upon careful preoperative evaluation of these aneurysms using sophisticated diagnostic methods.

Adolescent↗

[Extradural temporopolar approach for giant pituitary adenomas invading the cavernous sinus and parasellar regions].

OBJECTIVE: An extradural temporopolar approach has recently been used in the treatment of the parasellar, infrachiasmatic, or intracavernous regions. In this approach, the temporal (superficial) dural layer is separated from the deep layer (inner cavernous membrane) to expose the cavernous sinus extradurally. We report our experiences with 5 cases in which a giant pituitary adenoma invading the cavernous sinus and parasellar regions was resected via the extradural temporopolar approach. PATIENTS AND METHODS: Between January 1995 and December 1997, 60 patients with pituitary adenomas were operated on at Okayama University Hospital. The extradural temporopolar approach was used for 5 patients who had a giant pituitary adenoma invading the cavernous sinus and parasellar regions. The 5 patients were women aged from 32 to 62 years and presented with a visual dysfunction. Four patients had hormonally non-functioning pituitary adenomas and one had a growth-hormone secreting pituitary adenoma. RESULTS: The operations resulted in 1 total, 3 subtotal and 1 partial removal. There was no operative mortality or major morbidity. Transient oculomotor palsy occurred in 2 cases postoperatively. This approach provided excellent exposure of the tumor, relevant cranial nerves and arteries in and around the cavernous sinus through extradural retraction of the temporal lobe, allowing for sufficient resection of the intracavernous and parasellar portion of the tumor. Tumors invading the inferior portion of the clivus or the contralateral cavernous sinus could not be removed through this approach. CONCLUSION: Our findings suggest that the extradural temporopolar approach is useful for resection of giant pituitary adenomas invading the cavernous sinus and parasellar regions.

Adenoma↗

Long-term enhanced chromaffin cell survival and behavioral recovery in hemiparkinsonian rats with co-grafted polymer-encapsulated human NGF-secreting cells.

The transplantation of genetically modified cells represents one potential means of delivering trophic factors to the brain to support the survival of host neurons and to increase the survival of co-grafted cells. The present study examined the ability of encapsulated baby hamster kidney (BHK) fibroblasts, which were genetically modified to produce human nerve growth factor (hNGF), to provide long-term trophic support to co-grafted adrenal chromaffin cells. Following polymer encapsulation, BHK-hNGF cells were grafted into the striatum of hemiparkinsonian rats together with unencapsulated adrenal medullary chromaffin cells. Secretion of hNGF from the encapsulated cells, morphology of these cells, apomorphine-induced rotational behavior of the host animals, and survival of the co-grafted chromaffin cells were examined 1, 6, and 12 months after transplantation. Analysis of retrieved capsules revealed that the BHK cells survived and continued to release hNGF at a level of 2-3 ng/day even 12 months after transplantation. Although the animals receiving adrenal medulla alone did not show recovery of apomorphine-induced rotational behavior, the animals receiving adrenal medulla intrastriatal hNGF-secreting cells showed a significant decrease (40-50%) in apomorphine-induced rotation within 1 month postimplantation that remained stable for the 12-month test period. Tyrosine hydroxylase immunocytochemistry further revealed that while survival of chromaffin cells without hNGF support was poor, co-grafting of adrenal medulla and BHK-hNGF cells dramatically 926- to 32-fold) increased chromaffin cell survival 1, 6, and 12 months after transplantation. These results demonstrate that (1) encapsulated BHK cells survive for extended periods of time in vivo while continuing to secrete hNGF, (2) the continued secretion of hNGF provides trophic support for co-grafted adrenal chromaffin cells, and (3) the increased chromaffin cell survival is associated with long-term, stable behavioral recovery. These data further support the potential use of this approach for treating Parkinson's disease.

Adrenal Medulla↗

Three-dimensional analysis of vasospastic major cerebral arteries in rats with the corrosion cast technique.

BACKGROUND AND PURPOSE: Although mice, rats, and other small animals are commonly used for molecular biology research, their use in the evaluation of cerebral vasospasm after subarachnoid hemorrhage is somewhat problematic because of the correspondingly small size of their cerebral vessels. We have already reported that the corrosion cast technique was useful for evaluating newly formed cerebral vessels in neural grafts in these small animals. In the present study we applied the corrosion cast technique to the evaluation of hemolysate-induced cerebral vasospasm in rats and performed three-dimensional analysis for comparison. The casting was done 10 minutes after the hemolysate injection, so that only acute "vasospasm" was assessed. METHODS: After withdrawal of 0.1 mL cerebrospinal fluid, 0.2 mL hemolysate (n = 9) or saline (n = 10) was injected into the cisterna magna of male Sprague-Dawley rats weighing between 300 and 350 g. Ten minutes later, perfusion of a semipolymerized casting medium was performed at an injection pressure of 100 to 120 mm Hg. The brains were immersed and corroded in 10% NaOH solution. After these procedures, the basilar artery as well as peripheral vessels was analyzed morphologically with scanning electron microscopy. Conventional histological analysis with the use of paraffin-embedded section with hematoxylin-eosin staining was also performed, and the results were compared with those for the corrosion cast methods. RESULTS: In the saline-injected group, SEM showed that the inner surface of the basilar artery was smooth and the form of the endothelial cell was printed on the surface of the cast. In the hemolysate-injected group, the basilar artery showed an apparent vasospasm over its entire length, and corrugation was observed on the inner surface of the basilar artery in a three-dimensional fashion. Higher magnification revealed that the nuclei of the endothelial cells were distorted. Local narrowing of the basilar artery and vasospasm in the arteries of the anterior circulation and in peripheral arteries were also observed. Measurement of the inner diameter of the basilar artery showed 37.8% contraction in the hemolysate-injected group compared with the saline-injected group by the corrosion cast method. This degree of vasospasm was similar to that observed by the conventional histological method. CONCLUSIONS: In this report we show that detailed three-dimensional observation in the rat can be performed qualitatively and quantitatively with the corrosion cast technique. We conclude that this method derives an accurate measurement of the diameter of rat major cerebral arteries and is more reliable for analyzing vasospasm in rats than angiography and other conventional procedures.

Animals↗

Penetration of the optic chiasm by a ruptured anterior communicating artery aneurysm. Case report.

There are few reports of anterior communicating artery aneurysms causing visual symptoms, and penetration of the optic chiasm by such aneurysms has not been reported. A 40-year-old man presented with the abrupt onset of left homonymous hemianopsia, right visual acuity disturbance (finger counting), and slight headache. Angiography disclosed a 7-mm anterior communicating artery aneurysm projecting inferiorly. After the neck of the aneurysm was clipped, the dome of the aneurysm was resected. The operation confirmed that the aneurysm had penetrated the right half of the optic chiasm and the thrombosed dome had also compressed the right optic tract. Although the aneurysm was successfully clipped, the visual disturbance persisted after surgery, suggesting that the damage to the visual pathways by aneurysm penetration was irreversible in this case.

Adult↗