Univ Lille Nord de France, F-59000, Lille, France.
Fluids Barriers CNS. 2012 Jun 29;9(1):11. doi: 10.1186/2045-8118-9-11.
The function of pericytes remains questionable but with improved cultured technique and the use of genetically modified animals, it has become increasingly clear that pericytes are an integral part of blood-brain barrier (BBB) function, and the involvement of pericyte dysfunction in certain cerebrovascular diseases is now emerging. The porcine stress syndrome (PSS) is the only confirmed, homologous model of malignant hyperthermia (MH) in veterinary medicine. Affected animals can experience upon slaughter a range of symptoms, including skeletal muscle rigidity, metabolic acidosis, tachycardia and fever, similar to the human syndrome. Symptoms are due to an enhanced calcium release from intracellular stores. These conditions are associated with a point mutation in ryr1/hal gene, encoding the ryanodine receptor, a calcium channel. Important blood vessel wall muscle modifications have been described in PSS, but potential brain vessel changes have never been documented in this syndrome.
In the present work, histological and ultrastructural analyses of brain capillaries from wild type and ryr1 mutated pigs were conducted to investigate the potential impairment of pericytes, in this pathology. In addition, brain pericytes were isolated from the three porcine genotypes (wild-type NN pigs; Nn and nn pigs, bearing one or two (n) mutant ryr1/hal alleles, respectively), and tested in vitro for their influence on the permeability of BBB endothelial monolayers.
Enlarged perivascular spaces were observed in ryr1-mutant samples, corresponding to a partial or total detachment of the astrocytic endfeet. These spaces were electron lucent and sometimes filled with lipid deposits and swollen astrocytic feet. At the ultrastructural level, brain pericytes did not seem to be affected because they showed regular morphology and characteristics, so we aimed to check their ability to maintain BBB properties in vitro. Our results indicated that pericytes from the three genotypes of pigs had differing influences on the BBB. Unlike pericytes from NN pigs, pericytes from Nn and nn pigs were not able to maintain low BBB permeability.
Electron microscopy observations demonstrated brain capillary modifications in PSS condition, but no change in pericyte morphology. Results from in vitro experiments suggest that brain pericytes from ryr1 mutated pigs, even if they are not affected by this condition at the ultrastructural level, are not able to maintain BBB integrity in comparison with pericytes from wild-type animals.
周细胞的功能仍存在疑问，但随着培养技术的改进和基因修饰动物的使用，越来越清楚的是，周细胞是血脑屏障（BBB）功能的一个组成部分，周细胞功能障碍在某些脑血管疾病中的参与作用正在显现。猪应激综合征（PSS）是兽医领域中唯一被确认的与恶性高热（MH）同源的模型。受影响的动物在屠宰时会经历一系列症状，包括骨骼肌僵硬、代谢性酸中毒、心动过速和发热，类似于人类综合征。这些症状是由于细胞内储存的钙释放增强所致。这些情况与编码兰尼碱受体（一种钙通道）的 ryr1/hal 基因的点突变有关。在 PSS 中已经描述了重要的血管壁肌肉改变，但在这种综合征中从未记录到潜在的脑血管变化。
在本工作中，对来自野生型和 ryr1 突变型猪的脑毛细血管进行了组织学和超微结构分析，以研究在这种病理学中周细胞的潜在损伤。此外，从三种猪基因型（野生型 NN 猪；携带一个或两个（n）突变 ryr1/hal 等位基因的 Nn 和 nn 猪）中分离脑周细胞，并在体外测试它们对 BBB 内皮单层通透性的影响。
在 ryr1 突变样本中观察到增大的血管周围空间，对应于星形胶质细胞足突的部分或完全分离。这些空间电子透明，有时充满脂质沉积和肿胀的星形胶质细胞足突。在超微结构水平上，脑周细胞似乎没有受到影响，因为它们表现出正常的形态和特征，所以我们旨在检查它们在体外维持 BBB 特性的能力。我们的结果表明，来自三种猪基因型的周细胞对 BBB 有不同的影响。与 NN 猪的周细胞不同，Nn 和 nn 猪的周细胞不能维持低 BBB 通透性。
电子显微镜观察表明，PSS 条件下存在脑毛细血管改变，但周细胞形态无变化。体外实验结果表明，来自 ryr1 突变猪的脑周细胞，即使在超微结构水平上不受这种情况的影响，也不能维持 BBB 的完整性，与来自野生型动物的周细胞相比。
