TBI is a significant global public health concern, affecting more than 69 million individuals annually (Dewan et al., 2019). Traffic accidents, sports and daily falls are the main causes of it (Taylor et al., 2017; Cournoyer and Hoshizaki, 2019; Gardner and Jhala, 2021; Richards, 2010). Patients with TBI require continuous medical care (Goldstein et al., 2001), placing a substantial financial burden on both families and society (Te Ao et al., 2014).

The strength of the mechanical load applied to the head significantly impacts the outcome of TBI (Li et al., 2011; Namjoshi et al., 2017; Hsieh et al., 2017). However, the results can vary considerably when the impact location differs, even at the same load strength. A notable example is that a lateral hook punch in boxing is more likely to knock down an opponent compared to a straight punch (Cournoyer and Hoshizaki, 2019). Similarly, lateral impacts are more likely to cause concussions than frontal impacts in rugby (Gardner and Jhala, 2021). In traffic accidents, lateral collisions at 30mph result in approximately eight times the fatality rate of frontal collisions (Richards, 2010). Consistent results have been observed in animal experiments, where temporo-parietal impacts in monkeys are more likely to induce concussions and prolonged comas compared to frontal impacts (Hodgson et al., 1983). These location-dependent differences may be attributed to the brain's structural nonlinear properties (Sullivan et al., 2014), highlighting that the importance of considering impact location. This consideration is crucial for understanding the mechanisms of brain injury, medical treatment, and developing protective devices.

Studies on the effects of impact location on TBI have primarily focused on cranial vertex (Zhou et al., 2020; Li et al., 2011; Wang et al., 2018; Namjoshi et al., 2014), temporal lobe (Tagge et al., 2018), and anterior impacts (Kilbourne et al., 2009), with the latter involving application of force to the rat's zygomatic bone to induce injury (Kilbourne et al., 2009). Cranial vertex impacts induce sagittal plane head acceleration, resulting in coma and deficits in motor function, cognition, and emotion (Li et al., 2011; Wang et al., 2018; Namjoshi et al., 2014). These behavioral changes are linked to damage in key brain regions, such as the hippocampus, as evidenced by inflammatory responses, axonal disruption, and other pathological alterations (Li et al., 2011; Wang et al., 2018; Namjoshi et al., 2014). In contrast, temporal lobe impacts cause horizontal plane head acceleration, leading primarily to motor balance deficits (Tagge et al., 2018). These deficits are associated with astrocyte proliferation in cortical areas and cellular damage in hippocampal regions (Tagge et al., 2018). When comparing brain injuries induced by cranial vertex and temporal lobe impacts, cranial vertex impacts result in more severe cognitive deficits in rats (Mychasiuk et al., 2016). Elevated levels of neuroinflammatory factors in the prefrontal cortex and hippocampus further support the severe cognitive effects of cranial vertex impacts (Mychasiuk et al., 2016). However, temporal lobe impacts lead to more extensive axonal damage in the pyramidal tract compared to cranial vertex impacts (Wang et al., 2024). Additionally, both human and rat finite element models have been extensively used to explore the potential link between the mechanical response of the brain following cranial vertex impacts and corresponding pathological outcomes (Zhang et al., 2001). This information provides valuable insights into the effects of impact strength and location on behavioral deficits and pathological changes in key brain regions.

Although studies on the effects of different impact locations on TBI have been conducted, they have largely focused on behavioral and pathological changes resulting from cranial vertex and temporal lobe impacts (Wang et al., 2018; Tagge et al., 2018). Comparative studies examining the differences in brain injury between these impact sites have primarily addressed specific aspects of head injury, such as the expression of inflammatory factors or their complementarity with head injury criteria (Wang et al., 2024). However, these studies have not quantified the relative contributions of impact location and impact strength to TBI outcomes, nor have they provided insights into the mechanisms underlying the consistency between behavioral deficits and pathological changes. In light of this, the present study aims to quantify the contribution rates of impact location and strength to TBI outcomes by comparatively analyzing behavioral and pathological differences between cranial vertex and temporal lobe impacts at varying impact strengths. Additionally, it seeks to explore the correlation between pathological changes and behavioral manifestations in key functional brain regions. This study holds significant value in understanding the mechanisms of head injury, proposing scientific evaluation criteria, and developing effective protection strategies.