Intranasal Treatment of Central Nervous System Dysfunction in Humans

Chapman, Colin D.; Frey, William H.; Craft, Suzanne; Danielyan, Lusine; Hallschmid, Manfred; Schiöth, Helgi B.; Benedict, Christian

doi:10.1007/s11095-012-0915-1

Cited by 271 publications

(205 citation statements)

References 99 publications

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“…In contrast, subcutaneously applied vasopressin had pro-convulsive effects [330] in agreement with the excitatory potential of this neuropeptide [331,332]. For concerns on the penetration of oxytocin and vasopressin through the blood-brain-barrier, they have also been successfully applied intranasally [333][334][335]. There are 4 mammalian receptors of oxytocin and vasopressin: oxytocin receptor (OTR), and vasopressin receptors 1a, 1b, and 2 (V 1a , V 1b , and V 2 ).…”

Section: Oxytocin and Vasopressinmentioning

confidence: 99%

Receptors of Peptides as Therapeutic Targets in Epilepsy Research

Dobolyi¹,

Kékesi²,

Juhász³

et al. 2014

CMC

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Neuropeptides are signaling molecules participating in the modulation of synaptic transmission. Neuropeptides are stored in dense core synaptic vesicles, the release of which requires profound excitation. Only in the extracellular space, neuropeptides act on G-protein coupled receptors to exert a relatively slow action both pre-and postsynaptically. Consequently, neuropeptide modulators are ideal candidates to influence epileptic tissue overexcited during seizures. Indeed, a number of neuropeptides have been implicated in epilepsy and many of them are considered to have endogenous neuroprotective actions. Neuropeptides, present in the hippocampus, the most frequent focus of seizures in temporal lobe epilepsy, received the largest attention as potential anti-epileptic substances. Hippocampal neuropeptides, somatostatin, neuropeptide Y, galanin, dynorphin, enkephalin, substance P, cholecystokinin, vasoactive intestinal polypeptide, and some neuropeptides, which are also hormones such as ghrelin, angiotensins, corticotropin-releasing hormone, adrenocorticotropin, thyrotropin-releasing hormone, oxytocin and vasopressin involved in epilepsy are discussed in the review article. Oral application of neuropeptides as drugs is typically not efficient because of low bioavailability: rapid degradation and insufficient penetration through the blood-brain barrier. Recent progress in the development of non-peptide agonists and antagonists of neuropeptide receptors as well as gene therapeutic approaches leading to the local production of neuropeptides within the central nervous system will also be discussed.

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Section: Oxytocin and Vasopressinmentioning

confidence: 99%

Receptors of Peptides as Therapeutic Targets in Epilepsy Research

Dobolyi¹,

Kékesi²,

Juhász³

et al. 2014

CMC

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“…Recently, the intranasal administra tion of BMSCs into lesioned brains of rodents has been reported. 5,9,12,13,22,24 After their administration by simple drops into the nostrils, BMSCs are thought to migrate into the brains through the olfactory nerve route or trigeminal ganglion route. From the point of view of minimizing in vasiveness, the intranasal route is thought to be the least invasive of all the routes mentioned above.…”

mentioning

confidence: 99%

Intranasal delivery of bone marrow stromal cells to spinal cord lesions

Ninomiya¹,

Iwatsuki²,

Ohnishi³

et al. 2015

SPI

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OBJECT The intranasal delivery of bone marrow stromal cells (BMSCs) or mesenchymal stem cells to the injured brains of rodents has been previously reported. In this study, the authors investigated whether BMSCs migrate to spinal cord lesions through an intranasal route and whether the administration affected functional recovery. METHODS Forty Sprague-Dawley rats that were subjected to spinal cord injuries at the T7–8 level were divided into 5 groups (injured + intranasal BMSC–treated group, injured + intrathecal BMSC–treated group, injured-only group, injured + intranasal vehicle–treated group, and injured + intrathecal vehicle–treated group). The Basso-Beattie-Bresnahan (BBB) scale was used to assess hind limb motor functional recovery for 2 or 4 weeks. Intralesionally migrated BMSCs were examined histologically and counted at 2 and 4 weeks. To evaluate the neuroprotective and trophic effects of BMSCs, the relative volume of the lesion cavity was measured at 4 weeks. In addition, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) levels in the CSF were evaluated at 2 weeks. RESULTS Intranasally administered BMSCs were confirmed within spinal cord sections at both 2 and 4 weeks. The highest number, which was detected in the intrathecal BMSC–treated group at 2 weeks, was significantly higher than that in all the other groups. The BBB score of the intranasal BMSC–treated group showed statistically significant improvements by 1 week compared with the control group. However, in the final BBB scores, there was a statistically significant difference only between the intrathecal BMSC–treated group and the control group. The cavity ratios in the BMSC-treated groups were smaller than those of the control groups, but the authors did not find any significant differences in the NGF and BDNF levels in the CSF among the treatment and control groups. CONCLUSIONS BMSCs reached the injured spinal cord through the intranasal route and contributed to the recovery of hind limb motor function and lesion cavity reduction. However, the effects were not as significant as those seen in the intrathecal BMSC–treated group.

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“…On the other hand, restriction of the entry of therapeutics into the CNS by BBB is one of the major reasons that causes treatment failure (38). Intranasal delivery of the therapeutics is a useful strategy to treat variety of CNS diseases such as AD by bypassing BBB (8). There is evidence that direct acute administration of insulin into the CNS may improve cognitional performance in AD (35).…”

Section: Discussionmentioning

confidence: 99%

Intranasal insulin treatment improves memory and learning in a rat amyloid-beta model of Alzheimer’s disease

Farzampour¹,

Majdi²,

Sadigh-Eteghad³

2016

Physiology International

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Recently, insulin has been used as a pro-cognitive agent for the potential treatment of Alzheimer's disease (AD), because of its ability to cross the brain-blood barrier (BBB) by a saturable transport system. This study has been designed to evaluate the effects of intranasal insulin regimen, as a bypass system of BBB, on spatial memory in amyloid-beta (Aβ) model of AD in rat. Unilateral infusion of Aβ 25-35 (10 nmol/2 μl/rat) into the lateral ventricular region of brain was used to produce a rat model of AD. After a 24-h recovery period, rats received insulin or vehicle via intraperitoneal or intranasal route (0.1, 0.2, and 0.3 IU) for 14 days. Memory function in rats was assessed by Morris water maze test, with 5 days of training and consequent probe test protocol. Different doses of intraperitoneal insulin did not have a significant effect on learning and memory in AD rats. However, intranasal insulin at doses of 0.2 and 0.3 IU improved the learning and memory in Aβ-received rats.In conclusion, intranasal insulin as a non-invasive strategy improves spatial learning and memory in AD model.

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Intranasal Treatment of Central Nervous System Dysfunction in Humans

Cited by 271 publications

References 99 publications

Receptors of Peptides as Therapeutic Targets in Epilepsy Research

Receptors of Peptides as Therapeutic Targets in Epilepsy Research

Intranasal delivery of bone marrow stromal cells to spinal cord lesions

Intranasal insulin treatment improves memory and learning in a rat amyloid-beta model of Alzheimer’s disease

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