Dopamine Regulates Angiogenesis in Normal Dermal Wound Tissues

Cutaneous wound healing is a normal physiological process and comprises different phases. Among these phases, angiogenesis or new blood vessel formation in wound tissue plays an important role. Skin is richly supplied by sympathetic nerves and evidences indicate the significant role of the sympathetic nervous system in cutaneous wound healing. Dopamine (DA) is an important catecholamine neurotransmitter released by the sympathetic nerve endings and recent studies have demonstrated the potent anti-angiogenic action of DA, which is mediated through its D2 DA receptors. We therefore postulate that this endogenous catecholamine neurotransmitter may have a role in the neovascularization of dermal wound tissues and subsequently in the process of wound healing. In the present study, the therapeutic efficacy of D2 DA receptor antagonist has been investigated for faster wound healing in a murine model of full thickness dermal wound. Our results indicate that treatment with specific D2 DA receptor antagonist significantly expedites the process of full thickness normal dermal wound healing in mice by inducing angiogenesis in wound tissues. The underlined mechanisms have been attributed to the up-regulation of homeobox transcription factor HoxD3 and its target α5β1 integrin, which play a pivotal role in wound angiogenesis. Since D2 DA receptor antagonists are already in clinical use for other disorders, these results have significant translational value from the bench to the bedside for efficient wound management along with other conventional treatment modalities

Dopamine Regulates Mobilization of Mesenchymal Stem Cells during Wound Angiogenesis

Angiogenesis is an important step in the complex biological and molecular events leading to successful healing of dermal wounds. Among the different cellular effectors of wound angiogenesis, the role of mesenchymal stem cells (MSCs) is of current interest due to their transdifferentiation and proangiogenic potentials. Skin is richly innervated by sympathetic nerves which secrete dopamine (DA) and we have recently shown that concentration of DA present in synaptic cleft can significantly inhibit wound tissue neovascularization. As recent reports indicate that MSCs by mobilizing into wound bed play an important role in promoting wound angiogenesis, we therefore investigated the effect of DA on the migration of MSCs in wound tissues. DA acted through its D2 receptors present in the MSCs to inhibit their mobilization to the wound beds by suppressing Akt phosphorylation and actin polymerization. In contrast, this inhibitory effect of DA was reversed after treatment with specific DA D2 receptor antagonist. Increased mobilization of MSCs was demonstrated in the wound site following blockade of DA D2 receptor mediated actions, and this in turn was associated with significantly more angiogenesis in wound tissues. This study is of translational value and indicates use of DA D2 receptor antagonists to stimulate mobilization of these stem cells for faster regeneration of damaged tissues

Earthquake swarms near eastern Himalayan Syntaxis along Jiali Fault in Tibet: A seismotectonic appraisal

The seismotectonic characteristics of ten repeated earthquake swarm sequence within a seismic cluster along Jiali Fault in eastern Himalayan Syntaxis (EHS) have been analysed. The swarms are spatially disposed in and around Yigong Lake (a natural lake formed by blocking of Yigong River by landslide) and are characterized by low magnitude, crustal events with low to moderate b values. Ms : mb discriminant functions though indicate anomalous nature of the earthquakes within swarm but are considered as natural events that occurred under condition of high apparent stress and stress gradients. Composite fault plane solutions of selected swarms indicate strike–slip sense of shear on fault planes; solution parameters show low plunging compression and tensional axes along NW–SE and NE–SW respectively with causative fault plane oriented ENE–WSW, dipping steeply towards south or north. The fault plane is in excellent agreement with the disposition and tectonic movement registered by right lateral Jiali Fault. The process of pore pressure perturbation and resultant ‘r–t plot’ with modelled diffusivity (D = 0.12 m2/s) relates the diffusion of pore pressure to seismic sequence in a fractured poro-elastic fluid saturated medium at average crustal depth of 15–20 km. The low diffusivity depicts a highly fractured interconnected medium that is generated due to high stress activity near the eastern syntaxial bent of Himalaya. It is proposed that hydro fracturing with respect to periodic pore pressure variations is responsible for generation of swarms in the region. The fluid pressure generated due to shearing and infiltrations of surface water within dilated seismogenic fault (Jiali Fault) are causative factors

Seismic hazard assessment of Kashmir and Kangra valley region, Western Himalaya, India

A complete earthquake catalogue of the Western Himalaya (latitudes 30°N–36°N and longitudes 72°E–78°E) for the period of 1501–2010 has been compiled with earthquake magnitude computed in moment magnitude (Mw) scale. Pre- and early twentieth century records of earthquake damage have been documented from rare and out of print publications. Seismotectonics and seismic hazard for Kohistan arc, Kashmir–Hazara Syntaxis, Nanga-Parbat (Western Syntaxis), Karakoram and Himachal Himalaya are discussed with special reference to 1905 Kangra and 2005 Muzaffarabad earthquakes. Analyses of spatio-temporal variation in b-value from the region indicate significant precursor prior to the 2005 Muzaffarabad earthquake; progressive rise of background b-value observed and the main shock locates close to relative high b-value domains. Regions surrounding the location of the 1905 Kangra earthquake also display such high b-value for the period of 2005–2010 that calls for closer scrutiny. Temporal analysis of b-value from the epicentral block of Muzaffarabad earthquake clearly showed a high–low b-value couplet of 1.45–0.72, which may be treated as a typical precursor before an imminent large earthquake. Gumbel extreme value statistics indicate probability of occurrence of an event of Mw > 7.0 within 50 years in the region

Slab tear and tensional fault systems in the Sunda–Andaman Benioff zone: implications on tectonics and potential seismic hazard

Transverse slab tear faults and longitudinal trench parallel extensional faults present on the top part of Benioff zone in Sunda–Andaman arc between latitude 6°–15°N and longitude 90°–98°E are marked by seismotectonic analysis using contemporary data related to regional tectonics, seismicity, centroid moment tensor (CMT) fault plane solutions, etc. Characteristics of ten numbers of transverse slab tear faults is taken from our previous studies, whereas four numbers of longitudinal trench parallel extensional faults are marked by the present study. These two sets of fault systems make high angle between them and tectonically complement each other. The disposition, origin, tectonic framework, depth of penetration and seismotectonic evaluations of the fault systems are analyzed. An effort is made to identify the potential seismic hazard in the zone between trench and forearc containing Andaman Group of Island

Calcium Permeable AMPA Receptor-Dependent Long Lasting Plasticity of Intrinsic Excitability in Fast Spiking Interneurons of the Dentate Gyrus Decreases Inhibition in the Granule Cell Layer

The local fast-spiking interneurons (FSINs) are considered to be crucial for the generation, maintenance, and modulation of neuronal network oscillations especially in the gamma frequency band. Gamma frequency oscillations have been associated with different aspects of behavior. But the prolonged effects of gamma frequency synaptic activity on the FSINs remain elusive. Using whole cell current clamp patch recordings, we observed a sustained decrease of intrinsic excitability in the FSINs of the dentate gyrus (DG) following repetitive stimulations of the mossy fibers at 30 Hz (gamma bursts). Surprisingly, the granule cells (GCs) did not express intrinsic plastic changes upon similar synaptic excitation of their apical dendritic inputs. Interestingly, pairing the gamma bursts with membrane hyperpolarization accentuated the plasticity in FSINs following the induction protocol, while the plasticity attenuated following gamma bursts paired with membrane depolarization. Paired pulse ratio measurement of the synaptic responses did not show significant changes during the experiments. However, the induction protocols were accompanied with postsynaptic calcium rise in FSINs. Interestingly, the maximum and the minimum increase occurred during gamma bursts with membrane hyperpolarization and depolarization respectively. Including a selective blocker of calcium-permeable AMPA receptors (CP-AMPARs) in the bath; significantly attenuated the calcium rise and blocked the membrane potential dependence of the calcium rise in the FSINs, suggesting their involvement in the observed phenomenon. Chelation of intracellular calcium, blocking HCN channel conductance or blocking CP-AMPARs during the experiment forbade the long lasting expression of the plasticity. Simultaneous dual patch recordings from FSINs and synaptically connected putative GCs confirmed the decreased inhibition in the GCs accompanying the decreased intrinsic excitability in the FSINs. Experimentally constrained network simulations using NEURON predicted increased spiking in the GC owing to decreased input resistance in the FSIN. We hypothesize that the selective plasticity in the FSINs induced by local network activity may serve to increase information throughput into the downstream hippocampal subfields besides providing neuroprotection to the FSINs. (c) 2014 Wiley Periodicals, Inc

Kinematics and strain rates of the Eastern Himalayan Syntaxis from new GPS campaigns in Northeast India

Newly acquired GPS data along transects across Himalaya in Eastern Himalayan Syntaxis (EHS) reveal a clockwise rotation of rigid micro-plate comprising part of Brahmaputra valley, NE Himalaya and Northern Myanmar that rotates about a pole located at 14.5°N, 100.8°E at an angular rate of 1.75 ± 0.12°/Myr. The EHS is being torn-off from the main Indian Plate as a rigid block around which the kinematic clockwise rotation of Tibetan GPS sites toward the Sichuan-Yunnan region occurs in the Eurasia fixed frame. The residual velocity field of the newly acquired data estimated after removing the rotation that minimizes the GPS rates around EHS show a clear NE motion of the EHS sites, indentation of the rigid Indian plate into a less rigid area of the Eurasian plate. Themost extensive EHS zones of compression and shortening are in the direction of indenter convergence, with average values ranging between ~50–100 nanostrain/year. Along the frontal segment of EHS, from NWto SE, the shortening rate is reduced from the local maximum value of 160 to ~80 nanostrain/year, thus indicating a possibly locked fault patch of Mishmi or Lohit thrusts, the southernmost part of segment activated during the large 1950 Assam earthquake, Mw 8.6. An elastic block-model was invoked to infer the average slip rates of sections around EHS and to estimate an average locking depth of ~15 km. The slip rate perpendicular to the locked sector of EHS reaches 32.4mm/year and permits to roughly infer a recurrence time of ~200 year for an earthquake as energetic as the 1950 Assam event.Published15-261T. Deformazione crostale attivaJCR Journa