Cochlear Pericyte Responses to Acoustic Trauma and the Involvement of Hypoxia-Inducible Factor-1α and Vascular Endothelial Growth Factor

Abstract

This study explored the effect of acoustic trauma on cochlear pericytes. Transmission electron microscopy revealed that pericytes on capillaries of the stria vascularis were closely associated with the endothelium in both control guinea pigs and mice. Pericyte foot processes were tightly positioned adjacent to endothelial cells. Exposure to wide-band noise at a level of 120 dB for 3 hours per day for 2 consecutive days produced a significant hearing threshold shift and structurally damaged blood vessels in the stria vascularis. Additionally, the serum protein, IgG, was observed to leak from capillaries of the stria vascularis, and pericytes lost their tight association with endothelial cells. Levels of the pericyte structural protein, desmin, substantially increased after noise exposure in both guinea pigs and mice with a corresponding increase in pericyte coverage of vessels. Increased expression levels of desmin were associated with the induction of hypoxia inducible factor (HIF)-1␣ and the up-regulation of vascular endothelial growth factor (VEGF). Inhibition of HIF-1␣ activity caused a decrease in VEGF expression levels in stria vascularis vessels. Blockade of VEGF activity with SU1498, a VEGF receptor inhibitor, significantly attenuated the expression of desmin in pericytes. These data demonstrate that cochlear pericytes are markedly affected by acoustic trauma and display an abnormal morphology. HIF-1␣ activation and VEGF up-regulation are important factors for the alteration of the pericyte structural protein desmin. (Am J Pathol

Perivascular-resident macrophage-like melanocytes in the inner ear are essential for the integrity of the intrastrial fluid–blood barrier

“…The in vivo results corroborate in vitro results showing that absence of PVM/Ms weakens the endothelial barrier. This finding also confirms previous findings that disruption of the intrastrial fluid-blood barrier results in significant hearing loss (7,10).…”

“…The integrity of the barrier is critical for maintaining inner ear homeostasis, especially for sustaining the endocochlear potential (EP), an essential driving force for hearing function (1)(2)(3)(4). Disruption of the barrier is closely associated with a number of hearing disorders, including autoimmune inner ear disease, noise-induced hearing loss, agerelated hearing loss, and several genetically linked diseases (5)(6)(7)(8)(9)(10). Despite the importance of the intrastrial fluid-blood barrier, little is understood about regulation of the barrier and the mechanisms that control its permeability.…”

Sudden sensorineural hearing loss: Is there a connection with inner ear electrolytic disorders? A literature review

“…Within this structure, there are also perivascular-resident cells, known as melanocyte-like macrophages that play a role in the regulation of the integrity of the intra-strial blood-labyrinth barrier situated between blood flow and the intrastrial region. 17 The blood-labyrinth barrier is important not only to prevent the influx of toxic substances into the inner ear, but also for inner-ear homeostasis itself. 18,19 It is composed of endothelial cells (connected to each other by tight junctions 20 ), an underlying basement membrane, a large number of pericytes, 21 and perivascular resident macrophages.…”

“…[13][14][15][16][17] The Na + -K + ATPase activity is also the most studied ion transportation system within the inner ear so far.…”

Recent Research Trend for Ménièreʼs Disease

“…Initial transmission electron microscopy (TEM) studies demonstrated that the BLB in the guinea pig stria vascularis and spiral ligament is composed of vascular endothelial cells (VECs) surrounded by a basement membrane 6 . More recent studies have noted that, in addition, the intrastrial BLB is composed of pericytes and perivascular-resident macrophage-like melanocytes [7][8][9][10][11] . The VECs line the interior surface of the blood vessels, connected by tight junctions, forming an interface between circulating blood and the rest of the vessel wall.…”