ABSTRACT
BACKGROUND: Narcolepsy type 1 (NT1, narcolepsy with cataplexy) is a disabling neurological disorder caused by loss of excitatory orexin neurons from the hypothalamus and is characterized by decreased motivation, sleep-wake fragmentation, intrusion of rapid-eye-movement sleep (REMS) during wake, and abrupt loss of muscle tone, called cataplexy, in response to sudden emotions. OBJECTIVE: We investigated whether subcortical stimulation, analogous to clinical deep brain stimulation (DBS), would ameliorate NT1 using a validated transgenic mouse model with postnatal orexin neuron degeneration. METHODS: Using implanted electrodes in freely behaving mice, the immediate and prolonged effects of DBS were determined upon behavior using continuous video-electroencephalogram-electromyogram (video/EEG/EMG) and locomotor activity, and neural activation in brain sections, using immunohistochemical labeling of the immediate early gene product c-Fos. RESULTS: Brief 10-s stimulation to the region of the lateral hypothalamus and zona incerta (LH/ZI) dose-responsively reversed established sleep and cataplexy episodes without negative sequelae. Continuous 3-h stimulation increased ambulation, improved sleep-wake consolidation, and ameliorated cataplexy. Brain c-Fos from mice sacrificed after 90 min of DBS revealed dose-responsive neural activation within wake-active nuclei of the basal forebrain, hypothalamus, thalamus, and ventral midbrain. CONCLUSION: Acute and continuous LH/ZI DBS enhanced behavioral state control in a mouse model of NT1, supporting the feasibility of clinical DBS for NT1 and other sleep-wake disorders.
Subject(s)
Cataplexy/physiopathology , Cataplexy/therapy , Deep Brain Stimulation/methods , Hypothalamus/physiology , Animals , Cataplexy/genetics , Disease Models, Animal , Electroencephalography/methods , Electromyography/methods , Female , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Narcolepsy/genetics , Narcolepsy/physiopathology , Narcolepsy/therapy , Sleep/physiologyABSTRACT
Objective To study the anatomic data of the first metatarsal dorsal artery and to provide anatomical basis for clinical tissue transplantation based on the first metatarsal dorsal artery.Methods The 16 adult cadaver specimens with 32 feet were dissected and meas-ured by vernier caliper.Then the anatomic data of the first metatarsal dorsal artery were analyzed.Results Through the examinations of 32 feet sample,the first metatarsal dorsal artery were classified into 5 types.Type Ⅰ:the first metatarsal dorsal artery runs at the surface of the first dorsal interosseous muscle (13 sides,40.6%).Type Ⅱ:the first metatarsal dorsal artery runs in the interior of the first dorsal interosse-ous muscle (11sides,34.4%).Type Ⅲ:the first metatarsal dorsal artery runs underneath the first dorsal interosseous muscle (6 sides, 18.8%).Type Ⅳ:the first metatarsal dorsal artery is slender (1 side,3.1%).TypeⅤ:the first metatarsal dorsal artery is absent (1 side, 3.1%).Distance relationship was measured between the first metatarsal bone and the first metatarsal dorsal artery:the vertical distance be-tween the origin of the posterior branch of the first metatarsal dorsal artery and base of the first metatarsal bone was (2.4 ±0.3)mm,the ver-tical distance between the origin of the posterior branch of the first metatarsal dorsal artery and head of the first metatarsal bone was (10.1 ±1.0)mm;the vertical distance between the origin of the anterior branch of the first metatarsal dorsal artery and the first metatarso-phalangeal joint was (7.6 ±2.7)mm.Conclusion The first metatarsal dorsal artery has clinical reference significance for the hands and feet’s trauma and skin flap transplantation such as thumb reconstruction.
