Prolonged Convection-enhanced Delivery into the Rat Brainstem

Occhiogrosso, G.; Edgar, Mark A.; Sandberg, David I.; Souweidane, Mark M.

doi:10.1227/01.neu.0000043696.83722.8d

Cited by 55 publications

(34 citation statements)

References 29 publications

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“…Local application of solutions in this manner is similar to convection-enhanced delivery. Numerous studies have shown that convection-enhanced delivery of molecules into the brain of rats, cats, primates, and humans did not result in any clinical deterioration, raised intracranial pressure, or histological evidence of disrupted cytoarchitecture other than at the site of cannula insertion (Occhiogrosso et al, 2003). What was often observed was pressure or dilution artifact due to local application of control solutions (saline or citrate) from cannula placed in proximity (50 -100 m) of the working electrode.…”

Section: Methodsmentioning

confidence: 99%

Second-by-Second Measures of l-Glutamate in the Prefrontal Cortex and Striatum of Freely Moving Mice

Hascup

Hascup²,

Pomerleau³

et al. 2007

J Pharmacol Exp Ther

123

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L-Glutamate (Glu) is the main excitatory neurotransmitter in the mammalian central nervous system, and it is involved in most aspects of normal brain function, including cognition, memory and learning, plasticity, and motor movement. Although microdialysis techniques have been used to study Glu, the slow temporal resolution of the technique may be inadequate to properly examine tonic and phasic Glu. Thus, our laboratory has developed an enzyme-based microelectrode array (MEA) with fast response time and low detection limits for Glu. We have modified the MEA design to allow for reliable measures in the brain of awake, freely moving mice. In this study, we chronically implanted the MEA in prefrontal cortex (PFC) or striatum (Str) of awake, freely moving C57BL/6 mice. We successfully measured Glu levels 7 days postimplantation without loss of MEA sensitivity. In addition, we determined resting (tonic) Glu levels to be 3.3 M in the PFC and 5.0 M in the Str. Resting Glu levels were subjected to pharmacological manipulation with tetrodotoxin (TTX) and DL-threo-␤-hydroxyaspartate (THA). TTX significantly (p Ͻ 0.05) decreased resting Glu by 20%, whereas THA significantly (p Ͻ 0.05) increased resting Glu by 60%. Taken together, our data show that chronic recordings of tonic and phasic clearance of exogenously applied Glu can be carried out in awake mice for at least 7 days in vivo, allowing for longer term studies of Glu regulation.

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Section: Methodsmentioning

confidence: 99%

Second-by-Second Measures of l-Glutamate in the Prefrontal Cortex and Striatum of Freely Moving Mice

Hascup

Hascup²,

Pomerleau³

et al. 2007

J Pharmacol Exp Ther

123

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“…A subsequent study by this group demonstrated that prolonged CED can safely achieve large volumes of distribution in the rat brainstem. 79 Slow infusion rates are generally used because high flow rates may increase intracranial pressure and may disrupt tissue architecture.…”

Section: New Therapeutic Perspective Strategiesmentioning

confidence: 99%

Treatment of diffuse intrinsic brainstem gliomas: failed approaches and future strategies

Frazier¹,

Lee²,

Thomale

et al. 2009

PED

125

107

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Diffuse intrinsic pontine gliomas constitute ~ 60–75% of tumors found within the pediatric brainstem. These malignant lesions present with rapidly progressive symptoms such as cranial nerve, long tract, or cerebellar dysfunctions. Magnetic resonance imaging is usually sufficient to establish the diagnosis and obviates the need for surgical biopsy in most cases. The prognosis of the disease is dismal, and the median survival is < 12 months. Resection is not a viable option. Standard therapy involves radiotherapy, which produces transient neurological improvement with a progression-free survival benefit, but provides no improvement in overall survival. Clinical trials have been conducted to assess the efficacy of chemotherapeutic and biological agents in the treatment of diffuse pontine gliomas. In this review, the authors discuss recent studies in which systemic therapy was administered prior to, concomitantly with, or after radiotherapy. For future perspective, the discussion includes a rationale for stereotactic biopsies as well as possible therapeutic options of local chemotherapy in these lesions.

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“…Firstly, convection-enhanced delivery is a method of local delivery that drives an infusate through the extracellular fluid in neural tissue using a continuous pressure gradient [61]. Experimental studies have shown that convection-enhanced delivery can achieve a local drug concentration 10,000-fold greater than that achieved by intravenous drug administration without causing significant systemic exposure [62, 63]. Secondly, local delivery of chemotherapeutic agents to the brainstem can be achieved via a cannulated screw attached to the skull of the animal [59].…”

Section: Future Directionsmentioning

confidence: 99%

Brainstem Tumors: Where Are We Today?

Recinos

Sciubba

Jallo³

2007

Pediatr Neurosurg

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Brainstem tumors comprise 10–20% of all pediatric central nervous system tumors. The management of these tumors has evolved dramatically in the past century. Once considered uniformly fatal, it is now known that brainstem tumors have distinguishing characteristics and do not behave identically. The focality and location of the lesion is determined from the clinical history, presentation, and associated imaging. Based on these findings, it is possible to predict the behavior of the tumor and choose an appropriate intervention. Focal lesions have a good prognosis and are treated operatively while diffuse lesions have a poor prognosis and are managed medically. This article reviews the current classification of brainstem tumors, current management options and future directions for the treatment of these rare tumors.

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Prolonged Convection-enhanced Delivery into the Rat Brainstem

Cited by 55 publications

References 29 publications

Second-by-Second Measures of l-Glutamate in the Prefrontal Cortex and Striatum of Freely Moving Mice

Second-by-Second Measures of l-Glutamate in the Prefrontal Cortex and Striatum of Freely Moving Mice

Treatment of diffuse intrinsic brainstem gliomas: failed approaches and future strategies

Brainstem Tumors: Where Are We Today?

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