Liposome-mediated transfer of the bcl-2 gene results in neuroprotection after in vivo transient focal cerebral ischemia in an animal model

Cao, Ye; Shibata, Toru; Ng, Rainov

doi:10.1038/sj.gt.3301676

Cited by 57 publications

(40 citation statements)

References 24 publications

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“…Liposomes condense DNA and carry it into cells by membrane fusion and endocytosis (Cao et al, 2002;Zou et al, 1999). The development of a more efficient liposome formulation makes liposome-mediated gene transfer promising in treating central nervous system injury (Yang et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Increased Expression of a Proline-Rich Akt Substrate (PRAS40) in Human Copper/Zinc-Superoxide Dismutase Transgenic Rats Protects Motor Neurons from Death after Spinal Cord Injury

Narasimhan

Saito

et al. 2007

J Cereb Blood Flow Metab

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The serine-threonine kinase, Akt, plays an important role in the cell survival signaling pathway. A proline-rich Akt substrate, PRAS40, has been characterized, and an increase in phospho-PRAS40 (pPRAS40) is neuroprotective after transient focal cerebral ischemia. However, the involvement of PRAS40 in the cell death/survival pathway after spinal cord injury (SCI) is unclear. Liposomemediated PRAS40 transfection was performed to study whether overexpression of pPRAS40 is neuroprotective. We further examined the expression of pPRAS40 after SCI by immunohistochemistry and Western blot using copper/zinc-superoxide dismutase (SOD1) transgenic (Tg) rats and wild-type (Wt) littermates. We then examined the relationship between PRAS40 and Akt by injection of LY294002, a phosphatidylinositol 3-kinase (PI3K) pathway inhibitor, or Akt inhibitor IV, a compound that inhibits Akt activation after SCI. Our data demonstrated that increased pPRAS40 resulted in survival of more motor neurons compared with control complementary DNA transfection. Phosphorylated PRAS40 increased in the Wt rats after SCI, whereas there was a greater and prolonged increase in the SOD1 Tg rats. Coimmunoprecipitation showed that binding of pPRAS40 with 14-3-3 increased 1 day after SCI in the Wt rats, whereas there was a significant increase in the Tg rats. The inhibitor studies showed that phospho-Akt and pPRAS40 were decreased after injection of LY294002 or Akt inhibitor IV. We conclude that an increase in pPRAS40 by transfection after SCI results in survival of motor neurons, and overexpression of SOD1 in the Tg rats results in an increase in endogenous pPRAS40 and a decrease in motor neuron death through the PI3K/Akt pathway.

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Section: Introductionmentioning

confidence: 99%

Increased Expression of a Proline-Rich Akt Substrate (PRAS40) in Human Copper/Zinc-Superoxide Dismutase Transgenic Rats Protects Motor Neurons from Death after Spinal Cord Injury

Narasimhan

Saito

et al. 2007

J Cereb Blood Flow Metab

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“…To circumvent these obstacles, gene delivery research also aimed at the development of non-viral gene delivery vectors. To date, there have been many available methods that are able to deliver plasmids to cells in vitro and in vivo, such as liposomes [27] , cationic polymers [28] , electro-gene-transfer [29] , ultrasound [30] and hydrodynamic [31] , but they have also many disadvantages, such as toxicity, relatively low transfection efficiency as compared to viral gene delivery vectors, tissue damage and difficulties of application in humans.…”

Section: Discussionmentioning

confidence: 99%

Transfection of mEpo gene to intestinal epitheliumin vivomediated by oral delivery of chitosan-DNA nanoparticles

Chen¹,

Yang²,

Li³

et al. 2004

WJG

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AIM:To prepare the chitosan-pmEpo nanoparticles and to study their ability for transcellular and paracellular transport across intestinal epithelia by oral administration. METHODS:ICR mice were fed with recombinant plasmid AAV-tetO-CMV-mEpo (containing mEpo gene) or pCMVβ (containing LacZ gene), whether it was wrapped by chitosan or no. Its size and shape were observed by transmission electron microscopy. Agarose gel electrophoresis was used to assess the efficiency of encapsulation and stability against nuclease digestion. Before and after oral treatmant, blood samples were collected by retro-orbital puncture, and hematocrits were used to show the physiological effect of mEpo. RESULTS:Chitosan was able to successfully wrap the plasmid and to protect it from DNase degradation. Transmission electron microscopy showed that freshly prepared particles were approximately 70-150 nm in size and fairly spherical. Three days after fed the chitosan-pCMVβ complex was fed, the mice were killed and most of the stomach and 30% of the small intestine were stained. Hematocrit was not modified in naive and 'naked' mEpo-fed mice, a rapid increase of hematocrit was observed during the first 4 days of treatment in chitosan-mEpo-fed animals, reaching 60.9±1.2% (P<0.01), and sustained for a week. The second feed (6 days after the first feed) was still able to promote a second hematocrit increase in chitosan-mEpo-fed animals, reaching 65.9±1.4% (P<0.01), while the second hematocrit increase did not appear in the 'naked' mEpo-second-fed mice. CONCLUSION:Oral chitosan-DNA nanoparticles can efficiently deliver genes to enterocytes, and may be used as a useful tool for gene transfer.

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“…), and arterial blood samples obtained via a femoral catheter were collected to measure pO 2 , pCO 2 and pH with a blood gas analyzer (AVL 990, AVL Co., Graz, Austria). Rectal temperature was maintained at 37 ± 0.5°C during surgery with a regulated heating lamp [24,25] . Rats with physiological variables in the normal range were subjected to transient focal cerebral ischemia induced by left MCAO as previously described [9,11] .…”

Section: Transient Mcao Rats Were Anesthetized Withmentioning

confidence: 99%

Bcl-2 enhances the formation of newborn striatal long-projection neurons in adult rat brain after a transient ischemic stroke

et al. 2012

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Objective It has been reported that B-cell lymphoma 2 (Bcl-2) enhances neurogenesis as well as supporting axonal growth after injury. In the present study, we investigated whether Bcl-2 overexpression plays a role in the formation of newborn striatonigral projection neurons in the adult rat brain after transient middle cerebral artery occlusion (MCAO). Methods We infused human Bcl-2-expressing plasmid (pBcl-2) into the lateral ventricle immediately after 30 min of MCAO, injected 5'-bromodeoxyuridine (BrdU) intraperitoneally to label proliferative cells, and microinjected fluorogold (FG) into the substantia nigra at 11 weeks of reperfusion followed by multiple immunostaining of striatonigral projection neurons at 12 weeks. Results We found that pBcl-2 treatment significantly increased the number of newborn neurons (BrdU + -NeuN + ) in the striatum ipsilateral to the MCAO. We further detected newborn striatonigral projection neurons (BrdU + -FG + -NeuN + ) in the ipsilateral striatum at 12 weeks. More interestingly, the number of newborn striatonigral projection neurons (BrdU + -FG + ) was significantly increased by pBcl-2 treatment compared to that by pEGFP, a control plasmid. Conclusion Taken together, we found that Bcl-2 overexpression in the brain enhanced the generation of newborn striatonigral projection neurons. This provides a potential strategy for promoting the reestablishment of neural networks and brain repair after ischemic injury.

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Liposome-mediated transfer of the bcl-2 gene results in neuroprotection after in vivo transient focal cerebral ischemia in an animal model

Cited by 57 publications

References 24 publications

Increased Expression of a Proline-Rich Akt Substrate (PRAS40) in Human Copper/Zinc-Superoxide Dismutase Transgenic Rats Protects Motor Neurons from Death after Spinal Cord Injury

Increased Expression of a Proline-Rich Akt Substrate (PRAS40) in Human Copper/Zinc-Superoxide Dismutase Transgenic Rats Protects Motor Neurons from Death after Spinal Cord Injury

Transfection of mEpo gene to intestinal epitheliumin vivomediated by oral delivery of chitosan-DNA nanoparticles

Bcl-2 enhances the formation of newborn striatal long-projection neurons in adult rat brain after a transient ischemic stroke

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