Animal models of traumatic brain injury

CLARITY reveals a more protracted temporal course of axon swelling and disconnection than previously described following traumatic brain injury

“…By 1 week to 1 month following CCI, on both gross and histological (H&E and LFB/CV) examination, significant and progressive cavitation of the lesion site could be observed (Figure D,E,H). Consistent with previous descriptions, measurements of brain atrophy demonstrated a significant and progressive loss of tissue out to 1‐month post‐injury (Figure F) . APP IHC revealed extensive axonal pathology with tortuous varicose profiles and extensive axonal bulbs at 6 hours to 1‐week post‐CCI in peri‐contusional cortex, underlying corpus callosum, hippocampus, as well as more minimally in the ipsilateral thalamus (Figure I).…”

“…Given both the biomechanical and neuropathological features of CCI, findings can most reasonably be extrapolated to the axonal pathology observed in contused human brain tissue. Specifically, CCI relies upon controlled contact loading to the dural surface to cause dynamic deformation of brain tissue over the course of ~10‐30 milliseconds to induce the primary pathology of focal hemorrhagic cortical contusion . Consistent with multiple previous reports , extensive peri‐contusional APP+ axonal pathology was observed immediately below the impact site, as well as more minimal axon damage in the underlying hippocampus and thalamus.…”

“…Specifically, CCI relies upon controlled contact loading to the dural surface to cause dynamic deformation of brain tissue over the course of ~10‐30 milliseconds to induce the primary pathology of focal hemorrhagic cortical contusion . Consistent with multiple previous reports , extensive peri‐contusional APP+ axonal pathology was observed immediately below the impact site, as well as more minimal axon damage in the underlying hippocampus and thalamus. Much of the early axonal pathology is likely caused by the primary compressive forces caused by impact and associated downstream cascades.…”

CLARITY reveals a more protracted temporal course of axon swelling and disconnection than previously described following traumatic brain injury

“…By 1 week to 1 month following CCI, on both gross and histological (H&E and LFB/CV) examination, significant and progressive cavitation of the lesion site could be observed (Figure D,E,H). Consistent with previous descriptions, measurements of brain atrophy demonstrated a significant and progressive loss of tissue out to 1‐month post‐injury (Figure F) . APP IHC revealed extensive axonal pathology with tortuous varicose profiles and extensive axonal bulbs at 6 hours to 1‐week post‐CCI in peri‐contusional cortex, underlying corpus callosum, hippocampus, as well as more minimally in the ipsilateral thalamus (Figure I).…”

“…Given both the biomechanical and neuropathological features of CCI, findings can most reasonably be extrapolated to the axonal pathology observed in contused human brain tissue. Specifically, CCI relies upon controlled contact loading to the dural surface to cause dynamic deformation of brain tissue over the course of ~10‐30 milliseconds to induce the primary pathology of focal hemorrhagic cortical contusion . Consistent with multiple previous reports , extensive peri‐contusional APP+ axonal pathology was observed immediately below the impact site, as well as more minimal axon damage in the underlying hippocampus and thalamus.…”

“…Specifically, CCI relies upon controlled contact loading to the dural surface to cause dynamic deformation of brain tissue over the course of ~10‐30 milliseconds to induce the primary pathology of focal hemorrhagic cortical contusion . Consistent with multiple previous reports , extensive peri‐contusional APP+ axonal pathology was observed immediately below the impact site, as well as more minimal axon damage in the underlying hippocampus and thalamus. Much of the early axonal pathology is likely caused by the primary compressive forces caused by impact and associated downstream cascades.…”

Roadmap for Advancing Pre-Clinical Science in Traumatic Brain Injury

“…In humans, severe TBI typically involves extensive neuron death in the acute setting, whereas in a neuropathology study of mTBI where DAI was identified, cell death was absent 28 . Similar findings have been reported in animal models of TBI, with the extent of neuron death, or its absence also related to injury severity 20 . Through unknown mechanisms, the acute events of TBI can also trigger progressive neuron and glia cell death and axonal degeneration, leading to expanding loss of tissue volume in humans and rodent models.…”

Fingolimod improves diffuse brain injury by promoting AQP4 polarization and functional recovery of the glymphatic system

“…[2][3][4] DBI causes changes in vital signs and loss of consciousness, and the mortality rate is much higher than that associated with CCI. 4,5 CCI results in wound bleeding, focal tissue deformation, and increased autophagosomes, as observed by pathological analyses. Conversely, DBI is pathologically characterized by diffuse degeneration and white matter bleeding.…”

CLARITY reveals a more protracted temporal course of axon swelling and disconnection than previously described following traumatic brain injury

“…By 1 week to 1 month following CCI, on both gross and histological (H&E and LFB/CV) examination, significant and progressive cavitation of the lesion site could be observed (Figure D,E,H). Consistent with previous descriptions, measurements of brain atrophy demonstrated a significant and progressive loss of tissue out to 1‐month post‐injury (Figure F) . APP IHC revealed extensive axonal pathology with tortuous varicose profiles and extensive axonal bulbs at 6 hours to 1‐week post‐CCI in peri‐contusional cortex, underlying corpus callosum, hippocampus, as well as more minimally in the ipsilateral thalamus (Figure I).…”

“…Given both the biomechanical and neuropathological features of CCI, findings can most reasonably be extrapolated to the axonal pathology observed in contused human brain tissue. Specifically, CCI relies upon controlled contact loading to the dural surface to cause dynamic deformation of brain tissue over the course of ~10‐30 milliseconds to induce the primary pathology of focal hemorrhagic cortical contusion . Consistent with multiple previous reports , extensive peri‐contusional APP+ axonal pathology was observed immediately below the impact site, as well as more minimal axon damage in the underlying hippocampus and thalamus.…”

“…Specifically, CCI relies upon controlled contact loading to the dural surface to cause dynamic deformation of brain tissue over the course of ~10‐30 milliseconds to induce the primary pathology of focal hemorrhagic cortical contusion . Consistent with multiple previous reports , extensive peri‐contusional APP+ axonal pathology was observed immediately below the impact site, as well as more minimal axon damage in the underlying hippocampus and thalamus. Much of the early axonal pathology is likely caused by the primary compressive forces caused by impact and associated downstream cascades.…”

Roadmap for Advancing Pre-Clinical Science in Traumatic Brain Injury

“…In humans, severe TBI typically involves extensive neuron death in the acute setting, whereas in a neuropathology study of mTBI where DAI was identified, cell death was absent 28 . Similar findings have been reported in animal models of TBI, with the extent of neuron death, or its absence also related to injury severity 20 . Through unknown mechanisms, the acute events of TBI can also trigger progressive neuron and glia cell death and axonal degeneration, leading to expanding loss of tissue volume in humans and rodent models.…”

Fingolimod improves diffuse brain injury by promoting AQP4 polarization and functional recovery of the glymphatic system

“…[2][3][4] DBI causes changes in vital signs and loss of consciousness, and the mortality rate is much higher than that associated with CCI. 4,5 CCI results in wound bleeding, focal tissue deformation, and increased autophagosomes, as observed by pathological analyses. Conversely, DBI is pathologically characterized by diffuse degeneration and white matter bleeding.…”

CLARITY reveals a more protracted temporal course of axon swelling and disconnection than previously described following traumatic brain injury

“…By 1 week to 1 month following CCI, on both gross and histological (H&E and LFB/CV) examination, significant and progressive cavitation of the lesion site could be observed (Figure D,E,H). Consistent with previous descriptions, measurements of brain atrophy demonstrated a significant and progressive loss of tissue out to 1‐month post‐injury (Figure F) . APP IHC revealed extensive axonal pathology with tortuous varicose profiles and extensive axonal bulbs at 6 hours to 1‐week post‐CCI in peri‐contusional cortex, underlying corpus callosum, hippocampus, as well as more minimally in the ipsilateral thalamus (Figure I).…”

“…Given both the biomechanical and neuropathological features of CCI, findings can most reasonably be extrapolated to the axonal pathology observed in contused human brain tissue. Specifically, CCI relies upon controlled contact loading to the dural surface to cause dynamic deformation of brain tissue over the course of ~10‐30 milliseconds to induce the primary pathology of focal hemorrhagic cortical contusion . Consistent with multiple previous reports , extensive peri‐contusional APP+ axonal pathology was observed immediately below the impact site, as well as more minimal axon damage in the underlying hippocampus and thalamus.…”

“…Specifically, CCI relies upon controlled contact loading to the dural surface to cause dynamic deformation of brain tissue over the course of ~10‐30 milliseconds to induce the primary pathology of focal hemorrhagic cortical contusion . Consistent with multiple previous reports , extensive peri‐contusional APP+ axonal pathology was observed immediately below the impact site, as well as more minimal axon damage in the underlying hippocampus and thalamus. Much of the early axonal pathology is likely caused by the primary compressive forces caused by impact and associated downstream cascades.…”

Roadmap for Advancing Pre-Clinical Science in Traumatic Brain Injury

“…In humans, severe TBI typically involves extensive neuron death in the acute setting, whereas in a neuropathology study of mTBI where DAI was identified, cell death was absent 28 . Similar findings have been reported in animal models of TBI, with the extent of neuron death, or its absence also related to injury severity 20 . Through unknown mechanisms, the acute events of TBI can also trigger progressive neuron and glia cell death and axonal degeneration, leading to expanding loss of tissue volume in humans and rodent models.…”

Fingolimod improves diffuse brain injury by promoting AQP4 polarization and functional recovery of the glymphatic system

“…[2][3][4] DBI causes changes in vital signs and loss of consciousness, and the mortality rate is much higher than that associated with CCI. 4,5 CCI results in wound bleeding, focal tissue deformation, and increased autophagosomes, as observed by pathological analyses. Conversely, DBI is pathologically characterized by diffuse degeneration and white matter bleeding.…”