Intranasal nerve growth factor attenuates tau phosphorylation in brain after traumatic brain injury in rats

Intranasal gene delivery for treating Parkinson’s disease: overcoming the blood–brain barrier

“…Peptides, proteins, trophic factors Insulin [17] Alzheimer's disease [37][38][39][40] Psychosocial stress [41] IGF-1 [7] Huntington's disease [176] Hypoxic Ischemia [177,178] LPS-induced brain injury [179] b-IFN [8,18] --BDNF [19] Ischemia [67] GDNF [12] Parkinson's disease [30] NGF [20,21] Alzheimer's disease [76,77] TBI [78][79][80] Ischemia [81,82] Oxytocin --Aggression [53] Autism [47][48][49]58,180] Self-perception [50] Stress [52] Schizophrenia [55][56][57] Alcohol withdrawal [54] NAP [25] Alzheimer's disease [25,84,85] Mild cognitive impairment [86] Hypobaric hypoxia [87] Osteopontin [23,24] Ischemic stroke [23] Hemorrhagic stroke [24] Orexins [90] Narcolepsy [91][92][93] Olfactory dysfunction [94] NPY...…”

“…Intranasal NGF reduced amyloid precursor protein, Ab42 and tau hyperphosphorylation in the injured cortex of rats [78,79] and attenuated the brain edema following TBI [80]. It also improved cell survival [81], reduced in infarct volume and improved neurological function [82] in models of acute cerebral ischemia.…”

Investigational agents for treatment of traumatic brain injury

“…Intranasal delivery is a noninvasive and convenient method which successfully targets NGF to the CNS, bypassing the BBB and minimizing systemic exposure [91]. Intranasal NGF effectively attenuates the hyperphosphorylation of tau after TBI in rats, which may be mediated by an integrated signaling pathway related to nuclear factor-κB (NF-κB) [92], attenuates aquaporin-4-induced edema [93], and ameliorates beta-amyloid deposition [94]. A randomized, double-blind, placebo-controlled trial is underway to investigate the therapeutic effects of intranasal NGF in moderate and severe blunt TBI, with treatment starting between 24 to 72 hr post TBI, and continuing for 2 weeks (NCT01212679).…”

Advances in diagnosis, treatments, and molecular mechanistic studies of traumatic brain injury

“…NF-κB is also considered to play a significant part in the regulation of apoptosis (47). Several studies at different facilities have found that NF-κB, as a downstream element of a series of receptors such as toll-like receptor 4 (TLR-4) and tumor necrosis factor receptor-associated factor 6 (TRAF6), is activated in specimens of animal or human brains (48)(49)(50). Thus, NF-κB is considered to be a target by which to decrease inflammation and apoptosis after TBI.…”

“…An anti-seizure drug may be given during the first week to avoid any additional brain damage that might be caused by a seizure. Additional anti-seizure the up-regulation of NF-κB in brain tissue (47,50,51).…”