在動(dòng)物中進(jìn)行的一項(xiàng)新的研究報(bào)告說，一種以腦中難以接觸到的炎癥細(xì)胞為標(biāo)靶的新的基于納米技術(shù)的方法可能被用于治療出生后的腦癱,。
腦癱是由在子宮中或是在出生頭幾個(gè)月中對(duì)發(fā)育中的腦造成傷害所引起的一組疾病,，它會(huì)對(duì)許多腦部功能及神經(jīng)系統(tǒng)的功能造成損傷,，最顯著的是對(duì)運(yùn)動(dòng)技能的損傷,。在對(duì)損傷做出反應(yīng)時(shí)，腦子會(huì)激活被稱作小膠質(zhì)細(xì)胞和星形膠質(zhì)細(xì)胞的細(xì)胞,，這些細(xì)胞會(huì)對(duì)損傷進(jìn)行清理并清除細(xì)胞碎片,。不幸的是，這些細(xì)胞會(huì)過度反應(yīng)并開始破壞正常的周圍組織,，導(dǎo)致神經(jīng)發(fā)炎,。目前的消炎藥物必須在腦中繞過無數(shù)的屏障后才能到達(dá)小膠質(zhì)細(xì)胞和星形膠質(zhì)細(xì)胞（它們的靶細(xì)胞），因此這些藥物沒有達(dá)到它們?cè)撚械男Ч?/p>
如今,，Sujatha Kannan及其同事們展示,，被稱作樹狀分子的樹樣的分子可輕易地繞過這些屏障并有效地將藥物運(yùn)送至腦內(nèi)。樹狀分子看來可改善兔寶寶中腦癱癥狀,。有趣的是,，一但這些樹狀分子進(jìn)入腦內(nèi)，造成神經(jīng)發(fā)炎的細(xì)胞就會(huì)吞掉它們自己的毒藥（即含有藥物的分子）,，并因此停止了炎癥及其它有害的影響,。
研究人員給那些患有腦癱的兔寶寶帶有藥物的樹狀分子,，并顯示,，與未經(jīng)治療的兔子相比，僅在治療5天后,，這些兔子的運(yùn)動(dòng)功能就得到了大幅度的改善,。 結(jié)果暗示，這些樹狀分子可能會(huì)逆轉(zhuǎn)被診斷患有神經(jīng)炎癥的新生兒的腦損傷,。該小組下一步計(jì)劃觀察，在這一研究中所看到的運(yùn)動(dòng)功能的改善是否可持續(xù)到動(dòng)物的成年期,。
一篇相關(guān)的《焦點(diǎn)》文章討論了這些發(fā)現(xiàn)并指出,，用納米物質(zhì)治療腦損傷會(huì)在新生兒的診斷學(xué)、成像及藥物運(yùn)輸?shù)阮I(lǐng)域開辟新的前景,。(生物谷：Bioon.com)
doi:10.1126/scitranslmed.3003162
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Dendrimer-Based Postnatal Therapy for Neuroinflammation and Cerebral Palsy in a Rabbit Model
Sujatha Kannan1,2,*,†, Hui Dai1,2, Raghavendra S. Navath1,3, Bindu Balakrishnan1,2,*, Amar Jyoti1,2,*, James Janisse4, Roberto Romero1,† and Rangaramanujam M. Kannan
Cerebral palsy (CP) is a chronic childhood disorder with no effective cure. Neuroinflammation, caused by activated microglia and astrocytes, plays a key role in the pathogenesis of CP and disorders such as Alzheimer’s disease and multiple sclerosis. Targeting neuroinflammation can be a potent therapeutic strategy. However, delivering drugs across the blood-brain barrier to the target cells for treating diffuse brain injury is a major challenge. We show that systemically administered polyamidoamine dendrimers localize in activated microglia and astrocytes in the brain of newborn rabbits with CP, but not healthy controls. We further demonstrate that dendrimer-based N-acetyl-L-cysteine (NAC) therapy for brain injury suppresses neuroinflammation and leads to a marked improvement in motor function in the CP kits. The well-known and safe clinical profile for NAC, when combined with dendrimer-based targeting, provides opportunities for clinical translation in the treatment of neuroinflammatory disorders in humans. The effectiveness of the dendrimer-NAC treatment, administered in the postnatal period for a prenatal insult, suggests a window of opportunity for treatment of CP in humans after birth.
