Thursday, December 26, 2019

Focused ultrasound enhanced intranasal delivery of brain derived neurotrophic factor produces neurorestorative effects in a Parkinson's disease mouse model

Can your doctor and stroke hospital rub two neurons together and deduce that this could be an effective way to deliver BDNF?  BDNF is very useful in our recovery. Does your doctor know that and doing ANYTHING AT ALL about it? Or intranasal delivery?

Yes, this is in mice and for Parkinsons but do they have the ability to think outside the failed box of stroke recovery? Ask, and not politely, how they are going to get you 100% recovered. Anything less is complete failure on their part and the board of directors should have a policy to replace those failures. I take no prisoners.

 

Focused ultrasound enhanced intranasal delivery of brain derived neurotrophic factor produces neurorestorative effects in a Parkinson's disease mouse model


Author information

1
Department of Biomedical Engineering, Columbia University, New York, New York, USA.
2
Department of Pathology & Cell Biology, Columbia University, New York, New York, USA.
3
Department of the Center for Motor Neuron Biology and Disease, Columbia University, New York, New York, USA.
4
Department of the Columbia Translational Neuroscience Initiative, Columbia University, New York, New York, USA.
5
Department of Neurology, Columbia University, New York, New York, USA.
6
Department of Biomedical Engineering, Columbia University, New York, New York, USA. ek2191@columbia.edu.
7
Department of Radiology, Columbia University, New York, New York, USA. ek2191@columbia.edu.

Abstract

Focused ultrasound-enhanced intranasal (IN + FUS) delivery is a noninvasive approach that utilizes the olfactory pathway to administer pharmacological agents directly to the brain, allowing for a more homogenous distribution in targeted locations compared to IN delivery alone. However, whether such a strategy has therapeutic values, especially in neurodegenerative disorders such as Parkinson's disease (PD), remains to be established. Herein, we evaluated whether the expression of tyrosine hydroxylase (TH), the rate limiting enzyme in dopamine catalysis, could be enhanced by IN + FUS delivery of brain-derived neurotrophic factor (BDNF) in a toxin-based PD mouse model. Mice were put on the subacute dosing regimen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), producing bilateral degeneration of the nigrostriatal pathway consistent with early-stage PD. MPTP mice then received BDNF intranasally followed by multiple unilateral FUS-induced blood-brain barrier (BBB) openings in the left basal ganglia for three consecutive weeks. Subsequently, mice were survived for two months and were evaluated morphologically and behaviorally to determine the integrity of their nigrostriatal dopaminergic pathways. Mice receiving IN + FUS had significantly increased TH immunoreactivity in the treated hemisphere compared to the untreated hemisphere while mice receiving only FUS-induced BBB opening or no treatment at all did not show any differences. Additionally, behavioral changes were only observed in the IN + FUS treated mice, indicating improved motor control function in the treated hemisphere. These findings demonstrate the robustness of the method and potential of IN + FUS for the delivery of bioactive factors for treatment of neurodegenerative disorder.

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