Involvement of Denervated Midbrain-Derived Factors in the Formation of Ectopic Cortico-Mesencephalic Projection after Hemispherectomy.

Neuronal remodeling after brain injury is essential for functional recovery. After unilateral cortical lesion, axons from the intact cortex ectopically project to the denervated midbrain, but the molecular mechanisms remain largely unknown. To address this issue, we examined gene expression profiles in denervated and intact mouse midbrains after hemispherectomy at early developmental stages using mice of either sex, when ectopic contralateral projection occurs robustly. The analysis showed that various axon growth-related genes were upregulated in the denervated midbrain, and most of these genes are reportedly expressed by glial cells. To identify the underlying molecules, the receptors for candidate upregulated molecules were knocked out in layer 5 projection neurons in the intact cortex, using the CRISPR/Cas9-mediated method, and axonal projection from the knocked-out cortical neurons was examined after hemispherectomy. We found that the ectopic projection was significantly reduced when integrin subunit ß three or neurotrophic receptor tyrosine kinase 2 (also known as TrkB) was knocked out. Overall, the present study suggests that denervated midbrain-derived glial factors contribute to lesion-induced remodeling of the cortico-mesencephalic projection via these receptors.SIGNIFICANCE STATEMENT After brain injury, compensatory neural circuits are established that contribute to functional recovery. However, little is known about the intrinsic mechanism that underlies the injury-induced remodeling. We found that after unilateral cortical ablation expression of axon-growth promoting factors is elevated in the denervated midbrain and is involved in the formation of ectopic axonal projection from the intact cortex. Evidence further demonstrated that these factors are expressed by astrocytes and microglia, which are activated in the denervated midbrain. Thus, our present study provides a new insight into the mechanism of lesion-induced axonal remodeling and further therapeutic strategies after brain injury.

Spasticity and hyperselective neurectomy in the upper limb.

Spasticity is a complex pathology, both in terms of assessment and treatment. This article focuses on the clinical examination (objective, capacity, performance and function), which is key for choosing a treatment and can be helped by botulinum toxin injections. The treatment involves physical therapy, occupational therapy, medications and surgery. Neurectomy has been used in the upper limb since 1912 and is one of the therapeutic options for spasticity. This treatment is usually reserved for nonfunctional hands. Cadaver studies have helped us better understand nerve anatomy and improve the hyperselective neurectomy (HSN) technique. This article describes the history of neurectomy, how anatomical dissections apply to surgery, the HSN technique in the musculocutaneous nerve, median nerve and ulnar nerve and results of preliminary prospective studies. Spasticity, mobility, performance and function were evaluated a few months after HSN and about 12 months later to assess the permanence of the results in children and adult spastic patients. No matter the nerve or function targeted (elbow extension, wrist extension, or supination), spasticity was reduced with improvements in the functional House score and appeared stable at the last follow-up. HSN seems to be a good, reliable therapeutic option for spasticity, including functional hands.

Determinants of denervation-independent depletion of putamen dopamine in Parkinson's disease and multiple system atrophy.

BACKGROUND: Severe putamen dopamine depletion characterizes Parkinson's disease (PD) and multiple system atrophy (MSA). The extent of the depletion is greater than can be accounted for by loss of nigrostriatal dopaminergic terminals alone. We used putamen tissue levels and ratios of cysteinyl and parent catechols to explore possible denervation-independent abnormalities of dopamine synthesis and fate in PD and MSA. 5-S-Cysteinyldopa (Cys-DOPA) is produced from spontaneous oxidation of DOPA and 5-S-cysteinyldopamine (Cys-DA) from spontaneous oxidation of DA. METHODS: Post-mortem putamen tissue samples from 17 PD and 25 MSA patients and 30 controls were assayed for endogenous catechols including DA, its cytoplasmic metabolites (Cys-DA, 3,4-dihydroxyphenylacetic acid, 3,4-dihydroxyphenylethanol, and 3,4-dihydroxyphenylacetaldehyde), and tyrosine hydroxylation products proximal to DA (DOPA and Cys-DOPA). RESULTS: The PD and MSA groups did not differ in mean values of parent or cysteinyl catechols, and the data for the two groups were lumped. In the patients an index of vesicular storage of DA (the ratio of DA to the sum of its cytoplasmic metabolites) averaged 54% of control (p = 0.001), and an index of L-aromatic-amino-acid decarboxylase (LAAAD) activity (the ratio of DA and the sum of its cytoplasmic metabolites to the sum of DOPA + Cys-DOPA) averaged 21% of control (p < 0.0001). An index of innervation (the sum of DOPA + Cys-DOPA) averaged 63% of control (p = 0.01). INTERPRETATION: Based on patterns of parent and cysteinyl catechols in putamen, PD and MSA involve decreased vesicular uptake and decreased LAAAD activity in the residual dopaminergic terminals. The combination seems to contribute importantly to dopamine depletion in these diseases.

[Renal denervation. Current developments]. / Renale Denervation. Aktuelle Entwicklungen.

UNLABELLED: METHODICAL INNOVATION: Renal denervation is a catheter-based, endovascular procedure for the treatment of drug-resistant hypertension. The aim of the therapy is to lower the blood pressure < 140/90 mmHg. PERFORMANCE: Even after successful minimally invasive therapy patients usually continue to take three or more antihypertensive drugs. Currently there is no evidence that renal denervation is a good option for the treatment of well-controlled hypertension in order to dispense with antihypertensive drugs. In carefully selected patients the mean reduction in systolic and diastolic blood pressure after renal denervation is 25-30 mmHg and 10-15 mmHg, respectively. ACHIEVEMENTS: Procedure-related or device-related complications are rare. Ablation catheters from different manufactures differ greatly in handling properties; however, up to now there is no evidence for relevant differences in safety and efficacy between the devices available.