Gidö G, Kristián T, Siesjö B K
Laboratory for Experimental Brain Research, University Hospital, Lund, Sweden.
Neurobiol Dis. 1994 Nov;1(1-2):31-41. doi: 10.1006/nbdi.1994.0005.
Mechanisms causing gradual recruitment of damaged cells in the penumbra zone around the core of a focal ischaemic lesion may encompass irregularly occurring depolarization waves of the spreading depression (SD) type, each leading to transient loading of cells with calcium. It has been speculated that, when elicited in an underperfused or otherwise energy-compromised tissue, such depolarization waves lead to cell damage. We assessed under what conditions the calcium transients during KCl-induced SDs are prolonged, and explored if marked prolongation of the transients leads to brain damage. Cerebral blood flow (CBF) was reduced by marked hypocapnia. Tissue oxygenation was reduced by arterial hypoxia, without or with unilateral carotid artery occlusion, or by occlusion of the carotid arteries in normoxic, anaesthetized rats. In all animals the DC potential and extracellular calcium concentration (Ca2+e) were measured before and during a series of SDs. The animals were recovered for histopathological assessment. Hypoxia alone (Pao2, 32.5 +/- 3.8 mmHg) increased mean and total depolarization times, but repeated SDs elicited over 1.7 (+/-0.4) h failed to induce cell damage. Unilateral carotid artery occlusion further prolonged the SD waves but, in spite of total depolarization times of up to 40 min during 2 h, only two out of seven animals showed damage, localized to caudoputamen and parietal cortex, as well as to the subiculum, CA1 and CA3 sectors of the hippocampus. Bilateral carotid artery occlusion was associated with the most pronounced prolongation of the DC potential shifts and Ca2+ transients, with total depolarization times of up to 70 min. In spite of this, only four out of 13 animals showed brain damage and in two of these the damage was contralateral. The results justify modification of the hypothesis stating that SD-like depolarizations in the perifocal penumbra zone per se is what leads to gradual recruitment of such tissues in the infarction process. It is suggested that additional factors are required, such as a larger reduction in CBF, or the proximity of cells at risk to necrotic tissue.
在局灶性缺血性病变核心周围的半暗带区域，导致受损细胞逐渐募集的机制可能包括扩散性抑制（SD）类型的不规则去极化波，每一波均导致细胞短暂性钙负荷增加。据推测，当在灌注不足或以其他方式能量受损的组织中引发这种去极化波时，会导致细胞损伤。我们评估了在何种条件下氯化钾诱导的SD期间钙瞬变会延长，并探究瞬变的显著延长是否会导致脑损伤。通过显著低碳酸血症降低脑血流量（CBF）。通过动脉缺氧（无论有无单侧颈动脉闭塞）或在常氧、麻醉的大鼠中闭塞颈动脉来降低组织氧合。在所有动物中，在一系列SD之前和期间测量直流电位和细胞外钙浓度（Ca2+e）。动物恢复后进行组织病理学评估。单独缺氧（动脉血氧分压，32.5±3.8 mmHg）会增加平均和总去极化时间，但在1.7（±0.4）小时内引发的重复SD未能诱导细胞损伤。单侧颈动脉闭塞进一步延长了SD波，但尽管在2小时内总去极化时间长达40分钟，7只动物中只有2只出现损伤，损伤部位局限于尾状壳核、顶叶皮质以及海马的下托、CA1和CA3区。双侧颈动脉闭塞与直流电位变化和Ca2+瞬变的最显著延长相关，总去极化时间长达70分钟。尽管如此，13只动物中只有4只出现脑损伤，其中2只的损伤在对侧。这些结果证明有必要修正以下假设，即局灶周围半暗带区域类似SD的去极化本身就是梗死过程中此类组织逐渐募集的原因。有人提出还需要其他因素，例如更大程度的CBF降低，或危险细胞与坏死组织的接近程度。
