SUMMARY We have examined the incidence and size of infarction after occlusion of different portions of the rat middle cerebral artery (MCA) in order to define the reliability and predictability of this model of brain ischemia. We developed a neurologic examination and have correlated changes in neurologic status with the size and location of areas of infarction.The MCA was surgically occluded at different sites in six groups of normal rats. After 24 hr, rats were evaluated for the extent of neurologic deficits and graded as having severe, moderate, or no deficit using a new examination developed for this model. After rats were sacrificed the incidence of infarction was determined at histologic examination. In a subset of rats, the size of the area of infarction was measured as a percent of the area of a standard coronal section.Focal (1-2 nun) occlusion of the MCA at its origin, at the olfactory tract, or lateral to the inferior cerebral vein produced infarction in 13%, 67%, and 0% of rats, respectively (N = 38) and produced variable neurologic deficits. However, more extensive (3 or 6 mm) occlusion of the MCA beginning proximal to the olfactory tract -thus isolating lenticulostriate end-arteries from the proximal and distal supply -produced infarctions of uniform size, location, and with severe neurologic deficit (Grade 2) in 100% of rats (N = 17). Neurologic deficit correlated significantly with the size of the infarcted area (Grade 2, N = 17, 28 ± 5% infarction; Grade 1, N = 5, 19 ± 5%; Grade 0, N = 3, 10 ± 2%; p < 0.05).We have characterized precise anatomical sites of the MCA that when surgically occluded reliably produce uniform cerebral infarction in rats, and have developed a neurologic grading system that can be used to evaluate the effects of cerebral ischemia rapidly and accurately. The model will be useful for experimental assessment of new therapies for irreversible cerebral ischemia. Stroke Vol 17, No 3, 1986 DEVELOPMENT of a reproducible, reliable animal model of cerebral ischemia would allow the study of the pathophysiology of the lesion and the efficacy of various treatment modalities. Characteristics of models are based on similarities with syndromes of human cerebrovascular disease; 1 a review of available models of focal ischemic infarction has been published recently.2 Ideally, experimental occlusion with or without reperfusion is accompanied by predictable changes in blood flow and a consistent degree of infarction that produces lesions of predictable location and size.2 " 4 To insure that the neurologic examination is reliable, animals should be neurologically similar to humans in terms of behavior, sensory-motor integration, and relative amount of neocortex.5 These requirements are best met by occlusion of a single artery in subhuman primates.2 -6 However, primates are costly and difficult to maintain and therefore cannot be used by the majority of investigators who study cerebral ischemia.The laboratory rat is a well-studied, relatively inexpensive, and readily available animal that h...

Definition in the living premature infant of the anatomical and temporal characteristics of development of critical brain structures is crucial for insight into the time of greatest vulnerability of such brain structures. We used three-dimensional magnetic resonance imaging (3D MRI) and image-processing algorithms to quantitate total brain volume and total volumes of cerebral gray matter (GM), unmyelinated white matter (WM), myelinated WM, and cerebrospinal fluid (CSF) in 78 premature and mature newborns (postconceptional age, 29-41 weeks). Total brain tissue volume was shown to increase linearly at a rate of 22 ml/wk. Total GM showed a linear increase in relative intracranial volume of approximately 1.4% or 15 ml in absolute volume per week. The pronounced increase in total GM reflected primarily a fourfold increase in cortical GM. Unmyelinated WM was found to be the most prominent brain tissue class in the preterm infant younger than 36 weeks of postconceptional age. Although minimal myelinated WM was present in the preterm infant at 29 weeks, between 35 and 41 weeks an abrupt fivefold increase in absolute volume of myelinated WM was documented. Extracerebral and intraventricular CSF was readily quantitated by this technique and found to change minimally. The application of 3D MRI and tissue segmentation to the study of human infant brain from 29 to 41 weeks of postconceptional age has provided new insights into cerebral cortical development and myelination and has for the first time provided means of quantitative assessment in vivo of early human brain development.

We conclude that NIRS can be used in a noninvasive manner at the bedside to identify premature infants with impaired cerebrovascular autoregulation, that this impairment is relatively common in such infants, and that the presence of this impairment is associated with a high likelihood of occurrence of severe GMH-IVH/PVL.

Cerebral blood flow pressure-passivity results when pressure autoregulation is impaired, or overwhelmed, and is thought to underlie cerebrovascular injury in the premature infant. Earlier bedside observations suggested that transient periods of cerebral pressure-passivity occurred in premature infants. However, these transient events cannot be detected reliably by intermittent static measurements of pressure autoregulation. We therefore used continuous bedside recordings of mean arterial pressure (MAP; from an indwelling arterial catheter) and cerebral perfusion [using the nearinfrared spectroscopy (NIRS) Hb difference (HbD) signal) to detect cerebral pressure-passivity in the first 5 d after birth in infants with birth weight Ͻ1500 g. Because the Hb difference (HbD) signal [HbD ϭ oxyhemoglobin (HbO2) Ϫ Hb] correlates with cerebral blood flow (CBF), we used coherence between MAP and HbD to define pressure-passivity. We measured the prevalence of pressurepassivity using a pressure-passive index (PPI), defined as the percentage of 10-min epochs with significant low-frequency coherence between the MAP and HbD signals. Pressure-passivity occurred in 87 of 90 premature infants, with a mean PPI of 20.3%. Cerebral pressure-passivity was significantly associated with low gestational age and birth weight, systemic hypotension, and maternal hemodynamic factors, but not with markers of maternal infection. Future studies using consistent serial brain imaging are needed to define the relationship between PPI and cerebrovascular injury in the sick premature infant. C erebral pressure autoregulation maintains CBF relatively constant despite changes over a range of systemic blood pressures known as the autoregulatory plateau (1). Conversely, when changes in blood pressure result in concordant changes in CBF, the cerebral circulation is deemed "pressure passive." Current understanding is that cerebral pressurepassivity develops when changes in blood pressure exceed the capacity of the intact cerebral autoregulatory system or when the system is impaired by illness, injury, or vasoactive medications. Cerebral pressure-passivity is considered a risk factor for cerebrovascular injury in the sick premature infant (2-4). The current study extends our earlier work (3) using bedside NIRS to measure continuously cerebrovascular responses to spontaneous fluctuations in blood pressure. In our previous studies, we observed that cerebral pressure-passivity may wax and wane over relatively short periods in premature infants. To study the fluctuating nature of cerebral pressure-passivity and quantify its prevalence over time, we developed a continuous recording and analysis system because previously described techniques using intermittent static measurements (5-7) would be unable to measure the prevalence of fluctuating cerebral pressure-passivity over the highest risk for brain injury in premature infants. The principal aim of this technique is to make quantitative measurements of the prevalence of cerebral pressure-passivity rather...