High performance collection of cerebrospinal fluid in rats: Evaluation of erythropoietin penetration after osmotic opening of the blood–brain barrier

Ceaglio, Natalia; Orozco, Gustavo; Etcheverrigaray, Marina; Mattio, Mónica; Kratje, Ricardo; Perotti, Norma; Oggero, Marcos

doi:10.1016/j.jneumeth.2013.07.009

Cited by 10 publications

(10 citation statements)

References 31 publications

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“…Based on this evidence, it is reasonable to consider that ECA and, especially, LP administration can significantly improve brain resveratrol bioavailability to be 8.5 to 38.5 times higher with a dosage 6 % lower than that administered by intraperitoneal injection. Additionally, in comparison with ECA injection, LP would be preferable for brain delivery because it is easier to perform, is less invasive and, most importantly, delivers a higher intracranial drug bioavailability [41,42].…”

Section: Discussionmentioning

confidence: 99%

Diffusion Efficiency and Bioavailability of Resveratrol Administered to Rat Brain by Different Routes: Therapeutic Implications

Shu

Wang

et al. 2015

Neurotherapeutics

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Resveratrol possesses anti-tumor activities against central nervous system (CNS) tumors in vitro but has not yet been used clinically due to its low bioavailability, particularly in the CNS. This study thus aimed to elucidate brain bioavailability of trans-resveratrol by monitoring brain concentrations and dwell times following administration of resveratrol through intragastric, intraperitoneal, external carotid artery/ ECA and intrathecal routes. In parallel, we evaluated the biological responses of rat RG2 glioblastoma cells as well as RG2-formed rat intracranial glioblastomas treated with resveratrol via intrathecal administration. The results revealed that resveratrol was detected in rat brains except when administered systemically. Intrathecal administration of reseveratrol led to abundant apoptotic foci and increased staining of the autophagy proteins, LC-3 and Beclin-1 and shrinkage of the intracranial tumors. In conclusion, the BBB penetrability of resveratrol is remarkably increased by intracthecal administration. Regular short-term resveratrol treatments suppress growth and enhance autophagic and apoptotic activities of rat RG2 glioblastoma cells in vitro and in vivo. Therefore, intrathecal administration of resveratrol could be an optimal intervention approach in the adjuvant management of brain malignancies.

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Section: Discussionmentioning

confidence: 99%

Diffusion Efficiency and Bioavailability of Resveratrol Administered to Rat Brain by Different Routes: Therapeutic Implications

Shu

Wang

et al. 2015

Neurotherapeutics

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“…The intravenous injection of EPO is the most popular administration route in humans, and EPO administered in this manner has been reported to exert neuroprotective and neuroregenerative effects in numerous mouse and rat CNS injury models. 10,53,54 The worldwide use of EPO in the treatment of hematological diseases guarantees that it does not need further approval as a new drug; therefore, it can be more readily available to patients with CNS injuries than other drugs currently under development. 55 However, both nonhematopoietic and hematopoietic receptors coexist in the human body, with significant phylogenetic differences and heterogeneity.…”

Section: Intravenous Administrationmentioning

confidence: 99%

“…139 In contrast, the half-life of conventional rhEPO is 6-8 hours, 140 and the peak presence of rhEPO in the cerebrospinal fluid (CSF) occurs 2 hours after intravenous administration. 53 For optimal neuroprotection or regeneration, both the spontaneous breakdown of nanocarriers and the physiological nature of EPO must be balanced simultaneously.…”

Section: Spontaneous or Artificial Degradation Of Nanocarriers Into Smentioning

confidence: 99%

“…Following intravenous administration, EPO was observed in the same amounts as simultaneously injected mannitol for up to 8 hours in the CSF through the cisterna magna in a rat model. 53 Furthermore, chemical group-tagged EPO can also penetrate the BBB; for example, carbamylated EPO has been observed in the CSF for 4 to 24 hours following intravenous injection in a rat model. 54 Similar to EPO, nanocarriers can be transported through the BBB spontaneously in rat or mouse models in vivo; 115,152 for example, gold nanocarriers were observed at levels of 0.3-0.6 µg/1 g brain tissue/1 mg nanocarrier (up to 3.2 µg) in the frontal cortex, hippocampus and hypothalamus 24 hours after intraabdominal injection and 0.16 mg/L/60-105 mg nanocarrier in CSF 6 hours after injection in rats.…”

Section: Passage Through the Blood Brain Barriermentioning

confidence: 99%

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<p>Targeted Delivery of Erythropoietin Hybridized with Magnetic Nanocarriers for the Treatment of Central Nervous System Injury: A Literature Review</p>

Hwang¹

2020

IJN

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Although the incidence of central nervous system injuries has continued to rise, no promising treatments have been elucidated. Erythropoietin plays an important role in neuroprotection and neuroregeneration as well as in erythropoiesis. Moreover, the current worldwide use of erythropoietin in the treatment of hematologic diseases allows for its ready application in patients with central nervous system injuries. However, erythropoietin has a very short therapeutic time window (within 6-8 hours) after injury, and it has both hematopoietic and nonhematopoietic receptors, which exhibit heterogenic and phylogenetic differences. These differences lead to limited amounts of erythropoietin binding to in situ erythropoietin receptors. The lack of high-quality evidence for clinical use and the promising results of in vitro/in vivo models necessitate fast targeted delivery agents such as nanocarriers. Among current nanocarriers, noncovalent polymer-entrapping or polymer-adsorbing erythropoietin obtained by nanospray drying may be the most promising. With the incorporation of magnetic nanocarriers into an erythropoietin polymer, spatiotemporal external magnetic navigation is another area of great interest for targeted delivery within the therapeutic time window. Intravenous administration is the most readily used route. Manufactured erythropoietin nanocarriers should be clearly characterized using bioengineering analyses of the in vivo size distribution and the quality of entrapment or adsorption. Further preclinical trials are required to increase the therapeutic bioavailability (in vivo biological identity alteration, passage through the lung capillaries or the blood brain barrier, and timely degradation followed by removal of the nanocarriers from the body) and decrease the adverse effects (hematological complications, neurotoxicity, and cytotoxicity), especially of the nanocarrier.

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“…We collected CSF with a 1-mL syringe equipped with a 25G disposable needle (0.5×20 mm 2 ) as described previously. 29 First, we washed the rat's head with soap and water, removed the hair with a shaving blade, and fixed the head at an angle of about 135°. Then, the occipital crest was located, and the needle was carefully inserted from the caudal end at 30° to the body in the muscle gap at 3 mm below the occipital crest.…”

Section: Csf Samplingmentioning

confidence: 99%

Dextran-based biodegradable nanoparticles: an alternative and convenient strategy for treatment of traumatic spinal cord injury

Liu¹,

Quan²,

Li³

et al. 2018

IJN

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IntroductionAfter traumatic spinal cord injury (SCI), an inhibitory environment that contains chondroitin sulfate proteoglycans (CSPGs) is formed that prevents axonal regeneration and growth.Materials and methodsAs previously reported, local administration of Taxol® at a low concentration has shown promising abilities to promote axonal regeneration and downregulate inhibitory molecules after acute SCI. However, the application of an invasive miniosmotic pump to deliver Taxol and the Cremophor-related toxicity caused by Taxol limits the administration of Taxol.ResultsIn this study, the sustained release of paclitaxel (PTX) for 7 days was achieved by incorporating PTX into acetalated dextran (Ac-DEX) nanoparticles, and the prepared PTX-loaded Ac-DEX (PTX@Ac-DEX) nanoparticles promoted neurite extension in the presence of CSPGs. In a rat SCI model, both PTX@Ac-DEX and Taxol enhanced neural regeneration, inhibited CSPGs, protected the injured spinal cord, and improved locomotor recovery. Because of the sustained release of PTX, single administration of PTX@Ac-DEX showed equal therapeutic effect with Taxol, which need to be administered for seven days using a surgically implanted miniosmotic pump.ConclusionOverall, this study provides an effective and convenient strategy for SCI therapy, which can improve neurite extension across an inhibitory environment and avoid Cremophor-related toxicity caused by Taxol.

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High performance collection of cerebrospinal fluid in rats: Evaluation of erythropoietin penetration after osmotic opening of the blood–brain barrier

Cited by 10 publications

References 31 publications

Diffusion Efficiency and Bioavailability of Resveratrol Administered to Rat Brain by Different Routes: Therapeutic Implications

Diffusion Efficiency and Bioavailability of Resveratrol Administered to Rat Brain by Different Routes: Therapeutic Implications

<p>Targeted Delivery of Erythropoietin Hybridized with Magnetic Nanocarriers for the Treatment of Central Nervous System Injury: A Literature Review</p>

Dextran-based biodegradable nanoparticles: an alternative and convenient strategy for treatment of traumatic spinal cord injury

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