Characteristics of a rat model of an open craniocerebral injury at simulated high altitude

Abstract

To establish a rat model of an open craniocerebral injury at simulated high altitude and to examine the characteristics of this model. Rats were divided randomly into a normobaric group and a high-altitude group and their corresponding control groups. A rat model of an open craniocerebral injury was established with a nail gun shot. Simulated high-altitude conditions were established with a hypobaric chamber at 0.6 ATA to mimic pressure at an altitude of 4000 m. Mortality, brain water content (BWC), Evans blue content, pathology, regional cerebral blood flow (rCBF), partial pressure of brain tissue oxygen (PbtO2), and brainstem auditory-evoked potential were observed after injury. The mortality of the high-altitude group was significantly greater than that of the normobaric group within 72 h after injury (P<0.05). BWC and Evans blue content increased by 48 h after injury (P<0.05); pathological changes in damaged brains were more serious. In contrast, rCBF and PbtO2 had decreased markedly by 72 h (P<0.01); brainstem auditory-evoked potential values were significantly prolonged (P<0.05). Moreover, an inverse correlation between rCBF and BWC and a positive correlation between rCBF and PbtO2 were found. The rat model of an open craniocerebral injury at simulated high altitude can be established successfully using a nail gun shot and a hypobaric chamber. The injury characteristics at high altitude were more serious, rapid, and prolonged than those in the normobaric group.

Fig. 1

Comparison of the mortality rate of the HI and NI groups. The total mortality rate of the HI group within 72 h after injury was higher than that of the NI group (*P<0.05). HI, high-altitude injury group; NI, normobaric injury group.

Fig. 2

Pathological changes in rat brain tissue. (a) The entire coronal face of the projectile of the nail. An arrow indicates 3 mm away from the lesion center. (b–d): H&E staining; (e–g): Nissl staining. (b, e) Normal neurons in the cerebral cortex were found in the control group. (c, f) Fewer pathological injuries occurred in the NI group 48 h after injury, arrows indicate the same meaning as in (d, g). (d, g) Neuronal swelling, nuclear condensation, a reduction in Nissl body (arrow), and conspicuous edema of interstitium are shown 3 mm away from the lesion center in the HI group 48 h after injury. Scale bars for (b–g): ×200 magnification. (h) Normal blood–brain barrier. (i) Milder edema of perivascular occurred in the NI group (arrow). (j) Edema of perivascular was obviously observed 3 mm away from the lesion center 48 h after injury in the HI group (arrow). Asterisk indicates the lumen. Scale bar for transmission electron micrographs, ×6000. HI, high-altitude injury group; NI, normobaric injury group.

Fig. 3

(a) A graph showing changes in brain water content *P<0.05 and **P<0.01 versus the NI group at the same time point. (b) EB particles shown by fluorescence microscopy. (1) No blue-stained brain tissues were observed in the control group. (2) Fewer EB particles’ exudation (arrow) was observed in the NI group 12 h after injury. (3) More EB particles’ exudation (arrow) was observed in the HI group 12 h after injury. (c) Quantitative analysis of changes in the EB content. *P<0.05 versus the NI group at the same time point. EB, Evans blue; HI, high-altitude injury group; NI, normobaric injury group.

Fig. 4

(a) Changes in rCBF (flux) *P<0.05 and **P<0.01 versus reciprocal NI group at the same test point. (b) Inverse correlation between rCBF and BWC in the NI group, R=−0.892, P<0.01. (c) Inverse correlation between rCBF and BWC in the HI group. R=−0.941, P<0.01. BWC, brain water content; HI, high-altitude injury group; NI, normobaric injury group; rCBF, regional cerebral blood flow.

Fig. 5

(a) Comparison of changes in PbtO₂ in the normobaric and high-altitude groups (mmHg, x±s). **P<0.01 versus the NI group at the same time point. (b) Positive correlation between PbtO₂ and rCBF in the NI group, R=0.868, P<0.01. (c) Positive correlation between PbtO₂ and rCBF in the HI group. R=0.929, P<0.01. HI, high-altitude injury group; NI, normobaric injury group; PbtO₂, partial pressure of brain tissue oxygen; rCBF, regional cerebral blood flow.

Fig. 6

(a) Comparison of ipsilateral BAEP in the NI and HI groups. (b) Contralateral BAEP comparison in the NI and HI groups. *P<0.05 versus the NI group at the same time point. BAEP, brainstem auditory-evoked potential; HI, high-altitude injury group; NI, normobaric injury group.