isolation-culture-long-term-maintenance-primary-mesencephalic

Isolation, Culture and Long-Term Maintenance of Primary Mesencephalic Dopaminergic Neurons From Embryonic Rodent Brains

Degeneration of mesencephalic dopaminergic (mesDA) neurons is the pathological hallmark of Parkinson&#8217;s diseae. Study of the biological processes ...

A reduction in the local availability of nitric oxide (NO) may play a role in the etiology of chronic cerebral vasospasm after subarachnoid hemorrhage (SAH). We investigated the toxicity and efficacy of a locally delivered NO donor from a controlled-release polymer in preventing experimental cerebral vasospasm in rats and rabbits, respectively.

Prevention of experimental cerebral vasospasm by intracranial delivery of a nitric oxide donor from a controlled-release polymer: toxicity and efficacy studies in rabbits and rats.

Diethylenetriamine/nitric oxide (DETA/NO) has been shown to be an effective treatment for delayed posthemorrhagic vasospasm when released abluminally from ethylene-vinyl acetate copolymer (EVAc). However, the observed mortality associated with this drug warrants further investigation. To establish a maximum tolerable dose, this study evaluated the toxicity of DETA/NO released from EVAc in a dose-escalation series in cynomolgus monkeys (Macaca fascicularis).

Intracranial delivery of the nitric oxide donor diethylenetriamine/nitric oxide from a controlled-release polymer: toxicity in cynomolgus monkeys.

Most injuries to the neonatal brachial plexus occur acutely at birth, and are iatrogenic in origin. However, when weakness is accompanied by atrophy, nontraumatic etiologies should be considered. The differential diagnosis of chronic congenital brachial plexopathy includes cervical bone malformations, humeral osteomyelitis, varicella, and compression from various types of infantile tumors. An illustrative male infant delivered at 37 weeks of gestation with wasted musculature of the left upper arm, ipsilateral Horner's syndrome, and a hemidiaphragm is presented. On further examination, this patient manifested an underlying cervical tumor compressing the brachial plexus. Diagnostic steps leading to the pathologic identification of a solitary cervical myofibroma included physical examination, electromyography, radiographic imaging, and open biopsy. This report emphasizes the importance of differentiating acute from chronic congenital plexus palsy and of recognizing the possibility that infection or neoplasm may underlie the latter.

Infantile myofibromatosis: a nontraumatic cause of neonatal brachial plexus palsy.

Although several clinical trials utilizing the adeno-associated virus (AAV) type 2 serotype 2 (2/2) are now underway, it is unclear whether this particular serotype offers any advantage over others in terms of safety or efficiency when delivered directly to the CNS.

Recombinant adeno-associated virus type 2 pseudotypes: comparing safety, specificity, and transduction efficiency in the primate striatum. Laboratory investigation.

Obwohl mehrere klinische Studien, die unter Verwendung des Adeno-assoziierte Virus (AAV) Typs 2 2 Serotyp (2/2) sind jetzt im Gange, es ist unklar, ob diese bestimmten Serotyp keinen Vorteil gegen&uuml;ber anderen in Bezug auf Sicherheit und Effizienz beim direkt an die CNS bietet.

Rekombinante Adeno-assoziierte Virus Typ 2 Pseudotypes: Sicherheit, Spezifit&auml;t und Transduktion Effizienz im Striatum Primas vergleichen. Laboruntersuchung.

There are a number of emerging surgical indications for deep brain stimulation. We have shown that modulation of activity within motor, mood, and cognitive circuits has beneficial effects in patients with Parkinson's disease, treatment-resistant depression, and perhaps Alzheimer's type dementia. We review the rationale, safety, and efficacy for each of these indications, focusing on disease mechanisms and relevant data that are necessary to document therapeutic value in each case. The review closes with some thoughts on possible future directions for deep brain stimulation. It is likely that applications for deep brain stimulation will continue to expand as accumulating data establish its safety and efficacy profile in these and other conditions.

Deep brain stimulation emerging indications.

Es gibt eine Reihe von neuen chirurgischen Indikationen f&uuml;r Tiefe Hirnstimulation. Wir haben gezeigt, dass die Modulation der Aktivit&auml;t im Motor, Stimmung und kognitive Schaltungen wohltuende Wirkung bei Patienten mit Morbus Parkinson, Behandlung-resistente Depressionen und vielleicht Alzheimer Typ Demenz hat. Wir &uuml;berpr&uuml;fen die Begr&uuml;ndung, die Sicherheit und die Wirksamkeit f&uuml;r jede dieser Angaben Krankheitsmechanismen und relevanten Daten, die zum Dokument therapeutischen Wert in jedem Fall im Mittelpunkt. Die &Uuml;berpr&uuml;fung schlie&szlig;t mit einigen Gedanken &uuml;ber m&ouml;gliche Zukunftsperspektiven f&uuml;r Tiefe Hirnstimulation. Es ist wahrscheinlich, dass Anwendungen f&uuml;r Tiefe Hirnstimulation weiterhin anfallende Daten in diesen und anderen Bedingungen seine Sicherheit und Wirksamkeit Profil einrichten zu erweitern.

Deep Brain Stimulation aufstrebenden Indikationen.

Presentation to publication.

To examine whether multiple aneurysms located in the anterior cerebral artery (ACA), middle cerebral artery (MCA), or internal carotid artery (ICA) could be treated through single-stage, ipsilateral dual craniotomies.

Dual ipsilateral craniotomies through a single incision for the surgical management of multiple intracranial aneurysms.

The success of deep brain stimulation (DBS) surgery in treating medically refractory symptoms of some movement disorders has inspired further investigation into a wide variety of other treatment-resistant conditions. These range from disorders of gait, mood, and memory to problems as diverse as obesity, consciousness, and addiction. We review the emerging indications, rationale, and outcomes for some of the most promising new applications of DBS in the treatment of postural instability associated with Parkinson's disease, depression, obsessive-compulsive disorder, obesity, substance abuse, epilepsy, Alzheimer's-type dementia, and traumatic brain injury. These studies reveal some of the excitement in a field at the edge of a rapidly expanding frontier. Much work still remains to be done on basic mechanism of DBS, optimal target and patient selection, and long-term durability of this technology in treating new indications.

Novel applications of deep brain stimulation.

Surgical therapy for the secondary dystonias is generally perceived to be less effective than for primary disease. However, a number of case reports and small open series have recently appeared describing quite favorable outcomes following surgery for some nonprimary dystonias. We discuss surgical treatment options for this group of diverse conditions, including tardive dystonia, dystonic cerebral palsy, and certain heredodegenerative diseases in which deep brain stimulation and ablative lesions of the posteroventral pallidum have been shown to be effective. Other types of secondary dystonia respond less well to pallidal surgery, particularly when anatomical lesions of the basal ganglia are prominent on preoperative imaging. For these conditions, central baclofen delivery and botulinum toxin denervation may be considered. With optimal medical and surgical care, some patients with secondary dystonia have achieved reductions in disability and pain that approach those documented for primary dystonia.

Surgical treatment for secondary dystonia.

Pharmacological therapy has had limited success in the treatment of most major neurological diseases. This has motivated the development of a number of novel surgical approaches designed to ameliorate drug-induced side effects or pharmacoresistant symptoms. Deep brain stimulation (DBS) has been quite successful in controlling both the cardinal motor manifestation of Parkinson's disease and the side effects of prolonged levodopa therapy. This has encouraged the application of DBS technology to treat a number of other neurodegenerative conditions, including secondary dystonia associated with pantothenate kinase-associated neurodegeneration (PKAN, formerly Hallervorden-Spatz syndrome), chorea associated with Huntington's disease, and most recently, cognitive decline associated with Alzheimer's type dementia. We review the rationale, indications and outcomes of neuromodulation for selected neurodegenerative conditions. In addition to DBS, we discuss select small molecule and gene-based neuromodulatory approaches. Ongoing study of basic pathophysiological mechanisms may eventually allow directed primary prevention of some of these diseases, but until then, invasive neuromoduation will likely continue to play an ever-increasing role in the delivery of the most advanced care for patients with these debilitating conditions.

Neuromodulation for neurodegenerative conditions.

The field of functional neurosurgery has developed a number of recent innovative neuromodulatory approaches to treat disease that remains resistant to the best medical therapy. These include novel surgical techniques to intervene in motor and cognitive sequelae of refractory epilepsy, neurodegenerative disease, and certain psychiatric conditions. To a large extent, much of the innovation in our field continues to be driven by a systems-level understanding of the impact of disease on the brain. For example, several groups have exploited findings from neuroimaging work to identify a number of new potential neuromodulatory targets for the treatment of refractory depression. Ongoing discoveries at the cellular and molecular level promise targeted gene or drug delivery aimed at curing disease. Neurosurgeons will certainly remain at the forefront of translating these strategies into practical clinical applications. Several randomized trials are now underway to assess the safety and efficacy of a number of new approaches, and we will continue to acquire better knowledge of optimal patient selection, identification of the most effective neuromodulatory targets, and recognition of adverse effects as these studies progress.

Some recent trends and further promising directions in functional neurosurgery.

Surgical therapy for treatment-resistant obsessive compulsive disorder (OCD) remains an effective option for well-selected patients managed within a multidisciplinary setting. Historically, lesions within the limbic system have been used to control both obsessive thoughts and repetitive compulsions associated with this disease. We discuss classical targets as well as contemporary neuromodulatory approaches that have been shown to provide symptomatic relief. Recently, deep brain stimulation (DBS) of the anterior limb of the internal capsule/ventral striatum received Conformité Européene (CE) mark and Food and Drug Administration (FDA) approvals for treatment of intractable OCD. Remarkably, this is the first such approval for neurosurgical intervention in a strictly psychiatric indication in modern times. This target is discussed in detail along with alternative targets currently being proposed. We close with a discussion of gamma knife capsulotomy, a modality with deep historical roots. Further directions in the surgical treatment of OCD will require better preoperative predictors of postoperative responses, optimal selection of individualized targets, and rigorous reporting of adverse events and standardized outcomes. To meet these challenges, centers must be equipped with a multidisciplinary team and patient-centered approach to ensure adequate screening and follow up of patients with this difficult-to-treat condition.

Deep brain stimulation and ablation for obsessive compulsive disorder: evolution of contemporary indications, targets and techniques.

Specific vulnerability and degeneration of the dopaminergic neurons in the substantia nigra pars compacta of the midbrain is the pathological hallmark of Parkinson's disease. A number of transcription factors regulate the birth and development of this set of neurons and some remain constitutively expressed throughout life. These maintenance transcription factors are closely associated with essential neurophysiological functions and are required ultimately for the long-term survival of the midbrain dopaminergic neurons. The current review describes the role of two such factors, Nurr1 and engrailed, in differentiation, maturation, and in normal physiological functions including acquisition of neurotransmitter identity. The review will also elucidate the relationship of these factors with life, vulnerability, degeneration and death of mesencephalic dopaminergic neurons in the context of Parkinson's disease.

The lifelong maintenance of mesencephalic dopaminergic neurons by Nurr1 and engrailed.

Learning novel sequences constitutes an example of declarative memory formation, involving conscious recall of temporal events. Performance in sequence learning tasks improves with repetition and involves forming temporal associations over scales of seconds to minutes. To further understand the neural circuits underlying declarative sequence learning over trials, we tracked changes in intracranial field potentials (IFPs) recorded from 1142 electrodes implanted throughout temporal and frontal cortical areas in 14 human subjects, while they learned the temporal-order of multiple sequences of images over trials through repeated recall. We observed an increase in power in the gamma frequency band (30-100 Hz) in the recall phase, particularly in areas within the temporal lobe including the parahippocampal gyrus. The degree of this gamma power enhancement decreased over trials with improved sequence recall. Modulation of gamma power was directly correlated with the improvement in recall performance. When presenting new sequences, gamma power was reset to high values and decreased again after learning. These observations suggest that signals in the gamma frequency band may play a more prominent role during the early steps of the learning process rather than during the maintenance of memory traces.

Article	Year
Prevention of experimental cerebral vasospasm by intracranial delivery of a nitric oxide donor from a controlled-release polymer: toxicity and efficacy studies in rabbits and rats. Stroke; a journal of cerebral circulation\| PubMed ID: 12411661	2002
Intracranial delivery of the nitric oxide donor diethylenetriamine/nitric oxide from a controlled-release polymer: toxicity in cynomolgus monkeys. Neurosurgery\| PubMed ID: 16639332	2006
Infantile myofibromatosis: a nontraumatic cause of neonatal brachial plexus palsy. Pediatric neurology\| PubMed ID: 18805367	2008
Recombinant adeno-associated virus type 2 pseudotypes: comparing safety, specificity, and transduction efficiency in the primate striatum. Laboratory investigation. Journal of neurosurgery\| PubMed ID: 20950087	2011
Deep brain stimulation emerging indications. Progress in brain research\| PubMed ID: 21867796	2011
Presentation to publication. Journal of neurosurgery\| PubMed ID: 21961851	2011
Dual ipsilateral craniotomies through a single incision for the surgical management of multiple intracranial aneurysms. World neurosurgery\| PubMed ID: 22120339	2012
Novel applications of deep brain stimulation. Surgical neurology international\| PubMed ID: 22826807	2012
Surgical treatment for secondary dystonia. Movement disorders : official journal of the Movement Disorder Society\| PubMed ID: 23037556	2012
Neuromodulation for neurodegenerative conditions. Frontiers in bioscience (Elite edition)\| PubMed ID: 23277004	2013
Some recent trends and further promising directions in functional neurosurgery. Acta neurochirurgica. Supplement\| PubMed ID: 23652662	2013
Deep brain stimulation and ablation for obsessive compulsive disorder: evolution of contemporary indications, targets and techniques. The International journal of neuroscience\| PubMed ID: 24099662	2014
The lifelong maintenance of mesencephalic dopaminergic neurons by Nurr1 and engrailed. Journal of biomedical science\| PubMed ID: 24685177	2014
Decrease in gamma-band activity tracks sequence learning. Frontiers in systems neuroscience\| PubMed ID: 25653598	2014

Travis S. Tierney

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