Sniffing neuropeptides: a transnasal approach to the human brain

In the citing paper

“Born et al. reported that, after giving 40IU (80µg) in man, CSF levels rose within 10min from ~5pg/ml to ~10pg/ml, increasing to ~20pg/ml at 60min (17).”

In the citing paper

“Born et al. achieved plasma concentrations of 20pg/ml after giving 40IU vasopressin (17).These are higher than Robertson et al. reported for any patient, including those with pathologically elevated vasopressin secretion; in man, maximal urine concentrating ability is achieved at a vasopressin concentration of ~5pg/ml (33).”

In the citing paper

“Estimating the CSF volume as 300ml, it seems that ~4.5ng of vasopressin reached the CSF: 0.005% of the given dose -assuming that the rise was due to administered peptide and not endogenous release triggered indirectly.”

In the citing paper

“neuropeptides have been shown to gain access to the brain following intranasal administration (Born et al., 2002;Chang et al., 2012).”

In the citing paper

“Using this delivery route, substantial amounts of insulin are delivered into the brain5”

In the citing paper

“The intranasal dose administered in the present study has been associated with changes in central function in humans 58, and similar or smaller doses of oxytocin or vasopressin (24–48 IU for oxytocin; 40–80 IU for vasopressin) have been associated with elevations in peptide levels in the cerebrospinnal fluid in humans or macaques of no more than approximately 55 pg/ml in actual levels 70, 71, 72,”

In the citing paper

“Born and colleagues (5) showed that many neuropeptides crossed the blood-brain barrier when given intranasally.”

In the citing paper

“Since it was reported that the intranasal administration of neuropeptides increases their levels in cerebrospinal fluid (Born et al., 2002), there has been an upsurge of interest in experimental manipulations of central oxytocin in human populations (Bartz & Hollander, 2006; Campbell 2010; Heinrichs, von Dawans, & Domes, 2009).”

In the citing paper

“It is unlikely that the delay had any impact on the results, as previous research has shown that peptide concentrations in the cerebrospinal fluid remain relatively stable even 80 minutes after administration (Born et al., 2002).”

In the citing paper

“It is unlikely that the delay had any impact on the results, as previous research has shown that peptide concentrations in the cerebrospinal fluid remain relatively stable even 80 minutes after administration (Born et al., 2002).”

In the citing paper

“The discovery that intranasal administration of neuropeptides can reach the human central nervous system (17)”

In the citing paper

“Intranasal administration of vasopressin (AVP) and of OXT have been reported, in rats and mice, to increase the intracerebral concentration of these peptides, not only in the cerebrospinal fluid but also in selected brain regions (Born et al, 2002;Neumann et al, 2013).”

In the citing paper

“The acute effects of intranasal oxytocin are reported to persist until 60–80 min post-administration.33, 34”

In the citing paper

“It is estimated that only a small amount of intranasally administered oxytocin reaches the brain.33, 34, 46, 47”

In the citing paper

“The direct manipulation of neuropeptidergic central nervous signaling pathways can be achieved via the intranasal administration of peptides, which is known to bypass the blood–brain barrier and result in significant cerebrospinal fluid elevations in substance levels within 40 min, without the need for systemic infusion (14,15).”

In the citing paper

“the exact transnasal-CNS route remains unknown, and the proportion of OXT that actually reaches the CNS is exceptionally small relative to the given dose (Born et al., 2002; Chang et al., 2012; Striepens et al., 2013; Dal Monte et al., 2014; Modi et al., 2014).”

In the citing paper

“These results suggest that intranasal administration rapidly upregulates OT levels in the brain and plasma during the timeframe of behavioral testing, and that OT clears the system several hours after testing.”

In the citing paper

“Intranasally administered insulin is assumed to travel along olfactory and adjacent pathways and has been shown to rapidly accumulate in cerebrospinal fluid, indicating efficient transport to the brain.”

In the citing paper

“When acutely administered to humans at cumulative doses of up to 200 IU, IN insulin does not lead to large increases in systemic concentrations of the hormone 35 and appears to trigger side effects such as increases in cortisol and growth hormone only above this threshold.”

In the citing paper

“Experiments in healthy humans have shown that IN administered insulin bypasses the BBB and is detectable in CSF within 1 hour after administration.”