Traumatic brain injury (TBI) is one of the most common brain injuries caused by an external impact or pressure, such as rapid acceleration or deceleration, crushing, and projectile penetration. Following TBI, cognitive, physical, and psychosocial functions are impaired depending on the severity of the injury. To investigate TBI, several animal models of experimental traumatic brain injury have been developed. Out of these, the weight-drop injury model has been widely used to present diffused axonal injury and concussion. Weight-drop injury model provides an easy and inexpensive method for producing graded brain injuries in animals by simply dropping the weights from varying heights.
Weight drop models are relatively new techniques of TBI investigation, but the models are gaining tremendous success given their similarities to human TBI. These models could simulate the full spectrum of traumatic brain injury, ranging from mild concussion to severe TBI. Common TBI models, such as fluid percussion (FPI) and controlled cortical impact (CCI) produce focal brain contusion with little axonal injury. Whereas, weight drop models are used to reproduce diffuse brain injury (Kalish. & Whalen., 2016).
The weight-drop models use the gravitational force of the free-falling weight to generate focal or diffused brain injury. In this model, the scalp of anesthetized mice is shaved, and the periosteum is exposed by making an incision. A stainless steel helmet is fixed onto the skull with dental acrylic. This helmet distributes the kinetic energy over the brain, thereby preventing focal injury. The injury impact is delivered to the exposed skull or intact dura of the test animals. During the impact delivery, generally, silicon covered soft tips reduce the risk of skull fractures. For focal brain injury, the animals are placed on non-flexible platforms to minimize energy dissipation. In contrast, for diffused brain injury, the impact delivery is crucial as the effect is distributed over the skull and flexible platforms let the head accelerate (Albert. & Sirén., 2010).
The weight-drop injury device consists of a column of free-falling brass weights. Although the weights are enclosed in a Plexiglas tube, a slight left- or- right movement during its fall may potentially lateralize the impact causing uneven injury distribution. The device is equipped with an air-driven high-velocity impactor that is targeted to contact a steel disc implanted onto the rodent skull. Usually, the impactor has the same diameter as the steel disc, which is 10 mm. The top and middle surfaces of the device are made of acrylic glass and are used to hold a metal rod with a round plastic tip that penetrates to deliver the impact onto the animal’s skull. The bottom platform is constructed of iron, and a mouse’s head could be fixed on it to deliver falling weight into the targeted area of the skull (Cernak, 2005).
Protocol (Flierl. et al., 2009)
- Anesthetize the animal.
- Place the animal on a stereotaxic frame.
- Inject local anesthesia under the skull and open the scalp by making a midline incision to expose the skull bone, pull out the skin to expose the skull bone.
- Clean the skull bone by removing connective tissue and periosteum.
- Apply the tissue adhesive to attach the disk in the preferred position while using the midline and bregma sutures as reference points.
- Place the animal on a flexible bed and position the guide tube so that the weight hits the disk or the head of the animal.
- Release the weight from the set height.
- Immediately move the rat after the weight hits to prevent a second impact as the weight rebounds.
- Remove the steel disk and suture the scalp.
- Return the animal to a recovery cage.
Weight drop model – Surgery
- Carefully check the weight-drop mechanism of the device. Lubricate the metal rod with oil to ensure smooth gliding during the weight-drop procedure.
- Anesthetize the animals with isoflurane using a standard anesthetic machine.
- Monitor the depth of the anesthesia by toe pinch using tweezers.
- Weigh the animals to determine the amount of post-operative analgesics to be used.
- Disinfect the scalp using alcohol pads.
- Make a longitudinal midline incision (2.0–2.5 cm) with a scalpel (blade #10).
- Place the mouse onto the mobile platform of the weight-drop injury device. Place the device on a hard-surface bench, such as stone or marble, to minimize energy dissipation.
- Slowly advance the tip of the rod on the exposed mouse skull to determine the exact area of impact.
- Carefully adjust the mobile platform of the apparatus to determine the impact site.
- Push bilateral blocks under the mobile platform to stabilize the animal’s position for impact delivery.
- Retract the rod to the targeted position.
- Press the pedal of the device to deliver injury. The rod will fall freely on the skull.
- Immediately apply post-traumatic oxygen as the impact could lead to trauma-induced respiratory depression and death.
- Close the scalp by using standard suture material. The incision normally heals rapidly without wound complications.
- Inject fentanyl (0.05 mg per kg body weight, i.p.) as post-operative analgesia. Repeat its injection every 12 hours with 0.01 mg per kg body weight i.p. for continuous analgesia.
- Monitor initial neurological impairment per neurological severity score (NSS) 60 minutes after the injury, to assess the severity.
- Place the animals back into the cages kept in a temperature-controlled room with 12-hours light and dark cycles and monitor them every 6 hours.
- Immediately return the animals to cages at the end of the surgical procedures where access to water and food are freely available.
Mimicking traumatic brain injury (Kalish. & Whalen., 2016)
Weight drop models have been widely used to advance understanding of the pathophysiology of traumatic brain injury in rodents. These models have made it possible for researchers to replicate focal cerebral contusion as well as diffused brain injury characterized by axonal damage. Recently, closed head injury models with free head rotation have also been developed to model sports concussions. The weight-drop injury model efficiently reproduces t