scholarly journals Ischemic Neuroprotection by TRPV1 Receptor-Induced Hypothermia

2012 ◽  
Vol 32 (6) ◽  
pp. 978-982 ◽  
Author(s):  
Mirko Muzzi ◽  
Roberta Felici ◽  
Leonardo Cavone ◽  
Elisabetta Gerace ◽  
Alberto Minassi ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Mild Hypothermia ◽  
Unmet Need ◽  
Receptor Potential ◽  
Artery Occlusion ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Receptor ◽  
Promising Therapeutic Approach ◽  
Transient Receptor ◽  
Cerebral Artery Occlusion

Although treatment of stroke patients with mild hypothermia is a promising therapeutic approach, chemicals inducing prompt and safe reduction of body temperature are an unmet need. We measured the effects of the transient receptor potential vanilloid-1 (TRPV1) agonist rinvanil on thermoregulation and ischemic brain injury in mice. Intraperitoneal or intracerebroventricular injection of rinvanil induces mild hypothermia that is prevented by the receptor antagonist capsazepine. Both intraischemic and postischemic treatments provide permanent neuroprotection in animals subjected to transient middle cerebral artery occlusion (MCAo), an effect lost in mice artificially kept normothermic. Data indicate that TRPV1 receptor agonists are promising candidates for hypothermic treatment of stroke.

scholarly journals Chronic femoral artery occlusion augments exercise pressor reflex in decerebrated rats

2010 ◽  
Vol 299 (1) ◽  
pp. H106-H113 ◽  
Author(s):  
Hirotsugu Tsuchimochi ◽  
Jennifer L. McCord ◽  
Shawn G. Hayes ◽  
Satoshi Koba ◽  
Marc P. Kaufman
Keyword(s):  
Femoral Artery ◽  
Transient Receptor Potential ◽  
Pressor Response ◽  
Arterial Occlusion ◽  
Receptor Potential ◽  
Artery Occlusion ◽  
Transient Receptor Potential Vanilloid ◽  
Hindlimb Muscles ◽  
Pressor Reflex ◽  
Transient Receptor

In decerebrated rats, we determined the pressor and cardioaccelerator reflex responses to static contraction of hindlimb muscles whose femoral arteries were either occluded 72 h before contraction, occluded 3 min before contraction, or freely perfused. We found that the pressor reflex arising from the limb whose femoral artery was occluded for 72 h before contraction (32 ± 5 mmHg, n = 16) was significantly higher than the pressor reflex arising from the contralateral freely perfused limb (15 ± 3 mmHg, n = 16, P < 0.001) or than that arising from the contralateral limb whose femoral artery was occluded for only 3 min (17 ± 4 mmHg, n = 16, P < 0.001). Moreover, the pressor reflex arising from the limb whose femoral artery was occluded for 3 min before the start of contraction was not significantly different than that arising from the contralateral freely perfused limb ( n = 16, P = 0.819). The pressor component of the reflex arising from the limb whose femoral artery was occluded for 72 h was not changed by transient receptor potential vanilloid (TRPV) 1 receptor blockade with iodo-resiniferatoxin ( n = 15, P = 0.272), although the cardioaccelerator component was significantly reduced ( P = 0.005). In addition, the pressor response evoked by capsaicin injection in the femoral artery of the 72-h occluded limb was more than double that evoked from the freely perfused limb ( P = 0.026). We conclude that chronic (i.e., 72 h) but not acute (3 min), femoral arterial occlusion augments pressor reflex arising from contraction of hindlimb muscles and that TRPV1 receptors play little role in this augmentation.

scholarly journals Paclitaxel Induces Upregulation of Transient Receptor Potential Vanilloid 1 Expression in the Rat Spinal Cord

2020 ◽  
Vol 21 (12) ◽  
pp. 4341 ◽  
Author(s):  
Yukako Kamata ◽  
Toshie Kambe ◽  
Terumasa Chiba ◽  
Ken Yamamoto ◽  
Kazuyoshi Kawakami ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Mechanical Allodynia ◽  
Transient Receptor Potential ◽  
Thermal Hyperalgesia ◽  
Receptor Potential ◽  
Intrathecal Administration ◽  
Transient Receptor Potential Vanilloid ◽  
Rat Spinal Cord ◽  
Trpv1 Receptor ◽  
Transient Receptor

Painful peripheral neuropathy is a common adverse effect of paclitaxel (PTX) treatment. To analyze the contribution of transient receptor potential vanilloid 1 (TRPV1) in the development of PTX-induced mechanical allodynia/hyperalgesia and thermal hyperalgesia, TRPV1 expression in the rat spinal cord was analyzed after intraperitoneal administration of 2 and 4 mg/kg PTX. PTX treatment increased the expression of TRPV1 protein in the spinal cord. Immunohistochemistry showed that PTX (4 mg/kg) treatment increased TRPV1 protein expression in the superficial layers of the spinal dorsal horn 14 days after treatment. Behavioral assessment using the paw withdrawal response showed that PTX-induced mechanical allodynia/hyperalgesia and thermal hyperalgesia after 14 days was significantly inhibited by oral or intrathecal administration of the TRPV1 antagonist AMG9810. We found that intrathecal administration of small interfering RNA (siRNA) to knock down TRPV1 protein expression in the spinal cord significantly decreased PTX-induced mechanical allodynia/hyperalgesia and thermal hyperalgesia. Together, these results demonstrate that TRPV1 receptor expression in spinal cord contributes, at least in part, to the development of PTX-induced painful peripheral neuropathy. TRPV1 receptor antagonists may be useful in the prevention and treatment of PTX-induced peripheral neuropathic pain.

scholarly journals Cerebral ischemia induces TRPC6 via HIF1α/ZEB2 axis in the glomerular podocytes and contributes to proteinuria

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Krishnamurthy Nakuluri ◽  
Rajkishor Nishad ◽  
Dhanunjay Mukhi ◽  
Sireesh Kumar ◽  
Venkata P. Nakka ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Calcium Influx ◽  
Receptor Potential ◽  
Artery Occlusion ◽  
Ischemic Hypoxia ◽  
Elevated Expression ◽  
Filtration Apparatus ◽  
Transient Receptor ◽  
And Function ◽  
Cerebral Artery Occlusion

AbstractPodocytes are specialized cells of the glomerulus and key component of the glomerular filtration apparatus (GFA). GFA regulates the permselectivity and ultrafiltration of blood. The mechanism by which the integrity of the GFA is compromised and manifest in proteinuria during ischemic stroke remains enigmatic. We investigated the mechanism of ischemic hypoxia-induced proteinuria in a middle cerebral artery occlusion (MCAO) model. Ischemic hypoxia resulted in the accumulation of HIF1α in the podocytes that resulted in the increased expression of ZEB2 (Zinc finger E-box-binding homeobox 2). ZEB2, in turn, induced TRPC6 (transient receptor potential cation channel, subfamily C, member 6), which has increased selectivity for calcium. Elevated expression of TRPC6 elicited increased calcium influx and aberrant activation of focal adhesion kinase (FAK) in podocytes. FAK activation resulted in the stress fibers reorganization and podocyte foot process effacement. Our study suggests overactive HIF1α/ZEB2 axis during ischemic-hypoxia raises intracellular calcium levels via TRPC6 and consequently altered podocyte structure and function thus contributes to proteinuria.

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